2025-10-23T07:39:01-05:00 2025-03-31 881478669 CBIZ ADVISORS LLC 1899 L STREET NW 850 WASHINGTON DC 20036 990 2024-04-01 237337229 BRIGHTFOCUS FOUNDATION BRIG 3019483244 22512 GATEWAY CENTER DRIVE CLARKSBURG MD 20871 STACY PAGOS HALLER PRESIDENT/CEO 3019483244 2025-10-22 1 1 FRANK SMITH P00639053 2022274000 2025-10-22 2024 2025-03-06 01:10:19Z STACY PAGOS HALLER 22512 GATEWAY CENTER DRIVE CLARKSBURG MD 20871 89178037 0 X WWW.BRIGHTFOCUS.ORG X 1973 DC BRIGHTFOCUS FOUNDATION (BRIGHTFOCUS) SEEKS A WORLD FREE FROM DISEASES OF MIND AND SIGHT. 14 14 59 85 0 0 43373203 52879488 0 0 4702264 9840578 587403 703858 48662870 63423924 10704093 16943701 0 0 6876671 6479211 952781 1027076 13859870 27683861 28845021 46217406 53295009 2445464 10128915 63464652 65129292 37245915 28168825 26218737 36960467 X BRIGHTFOCUS FOUNDATION FUNDS EXCEPTIONAL RESEARCH WORLDWIDE TO DEFEAT ALZHEIMER'S DISEASE, MACULAR DEGENERATION, AND GLAUCOMA AND PROVIDES EXPERT INFORMATION ON THESE HEARTBREAKING DISEASES. PLEASE REFER TO SCHEDULE O FOR A COMPLETE OVERVIEW OF OUR MISSION. 0 0 21402299 10412240 ALZHEIMER'S DISEASE RESEARCH (ADR)PLEASE REFER TO SCHEDULE O FOR A COMPLETE DESCRIPTION OF THE ACCOMPLISHMENTS FOR ALZHEIMER'S DISEASE RESEARCH. 10955751 5329984 MACULAR DEGENERATION RESEARCH (MDR)PLEASE REFER TO SCHEDULE O FOR A COMPLETE DESCRIPTION OF THE ACCOMPLISHMENTS FOR MACULAR DEGENERATION RESEARCH. 2469629 1201477 NATIONAL GLAUCOMA RESEARCH (NGR) PLEASE REFER TO SCHEDULE O FOR A COMPLETE DESCRIPTION OF THE ACCOMPLISHMENTS FOR NATIONAL GLAUCOMA RESEARCH. 34827679 1 1 0 1 0 0 0 0 0 1 1 1 0 0 1 1 0 1 0 0 1 1 0 1 1 0 0 1 0 1 0 0 0 0 0 0 0 0 1 0 0 0 1 0 0 0 0 1 88 0 1 59 1 0 0 0 0 0 1 1 0 0 0 0 0 0 X 14 14 0 0 0 0 0 0 0 1 1 0 0 1 1 1 1 1 1 1 1 0 AK AL AR CA CT FL GA HI IL KS KY ME MD MA MI MN MO MS NC ND NH NJ NM NY OH OK OR PA RI SC TN UT VA WA WI WV X X X JONATHAN WALSH 3015569385 22512 GATEWAY CENTER DRIVE CLARKSBURG MD 20871 PATRICIA M STEWART CHAIR 10.00 X X 0 0 0 SCOTT KAISER MD SECRETARY UNTIL 06/24, VICE CHAIR 6.00 X X 0 0 0 THOMAS F FREDDO OD PHD DIRECTOR UNTIL 06/24, SECRETARY 6.00 X X 0 0 0 SHAWNA GOTTLIEB TREASURER 6.00 X X 0 0 0 CECILIA ARRADAZA VICE CHAIR UNTIL 06/24, DIRECTOR 6.00 X X 0 0 0 PAUL CAMPBELL DIRECTOR 5.00 X 0 0 0 HERBERT L DRAYTON III DIRECTOR 5.00 X 0 0 0 DANA GRIFFIN DIRECTOR 5.00 X 0 0 0 TONYA MATTHEWS PHD DIRECTOR 5.00 X 0 0 0 ANN SECLOW DIRECTOR 5.00 X 0 0 0 JAN M STOUFFER PHD DIRECTOR 6.00 X 0 0 0 ADAM MYERS DIRECTOR AS OF 04/24 5.00 X 0 0 0 JOHN PENN DIRECTOR AS OF 03/25 5.00 X 0 0 0 DALE YOUNG DIRECTOR AS OF 03/25 5.00 X 0 0 0 STACY PAGOS HALLER PRESIDENT/CEO 45.00 X 424828 0 46677 NANCY KEACH SR. VP, STRATEGIC PARTNERSHIPS 45.00 X 270157 0 51713 R BRIAN ELDERTON SR. VP, DEVELOPMENT 45.00 X 261323 0 40046 JONATHAN WALSH SVP, FINANCE & ADMINISTRATION 45.00 X 226786 0 4251 DIANE BOVENKAMP PHD VP, SCIENTIFIC AFFAIRS 45.00 X 196242 0 24358 KACI BAEZ - VP INTEGRATED MKTING & COMM. UNTIL 06/24 45.00 X 110647 0 8838 PREETI SUBRAMANIAN - PHD DIR OF SCIENT. PROGRAMS, VISION SCIENCE 40.00 X 139931 0 16400 LISA MORGAN SENIOR DIRECTOR, ANNUAL GIVING 40.00 X 135115 0 22867 SHARYN ROSSI - PHD DIR OF SCIENT. PROGRAMS, NEUROSCIENCE 40.00 X 125732 0 42143 JEFFREY HONAKER SR. MGR. OPS AND BUILDING 40.00 X 115469 0 33854 2006230 0 291147 12 0 1 0 RKD GROUP 35 PARKWOOD DRIVE SUITE 160 HOPKINTON MA 01748 PUBLIC AWARENESS CONSULTING & MATERIALS 12374028 ADSTRA LLC 750 COLLEGE ROAD EAST STE 201 PRINCETON NJ 08540 MAIL LIST RENTAL 1758266 DATA MANAGEMENT INC 160 STONE STREET STONEVILLE NC 27048 DATABASE MANAGEMENT 310839 ROYAL SONESTA CHICAGO DOWNTOWN 71 E WACKER DRIVE CHICAGO IL 60601 HOTEL CONFERENCE 219320 THE ROBERT JOSEPH GROUP 6901 ROCKLEDGE DRIVE BETHESDA MD 20817 FINANCE AND ACCOUNTING 213430 12 124297 222435 52532756 394954 52879488 1052357 1052357 370381 370381 565015 179056 385959 385959 385959 22404949 11871081 21893998 3593811 510951 8277270 8788221 8788221 30640 222435 87248 -56608 -56608 OTHER INCOME 900099 4126 4126 4126 63423924 0 0 10544436 13267808 13267808 3675893 3675893 1652825 975321 365576 311928 3413792 1685554 1263641 464597 327893 172202 105437 50254 735356 386193 236460 112703 349345 183468 112335 53542 71456 38524 25216 7716 118544 63911 41833 12800 1027076 1027076 241293 241293 1441677 1266242 147747 27688 2434520 1230126 1204394 1270619 658427 135325 476867 602095 326769 171648 103678 368766 214621 114177 39968 258884 221715 19208 17961 876230 820584 24020 31626 383185 383185 596953 332227 181264 83462 54674 25895 14298 14481 PUB. AWARENESS POSTAGE 9119632 4191654 528303 4399675 PUB. AWARENESS PRINTING 6362574 2938902 276015 3147657 PUB. AWARENESS COMP. 2744419 1277945 127580 1338894 LIST RENTAL 1899500 873698 92899 932903 53295009 34827679 4607460 13859870 X 19360619 8338957 982887 10038775 829628 3278680 8516562 6619066 6199054 9183959 23832 25908 28325 36763 998282 1557144 9283683 5312032 7847284 3971651 31237150 32437847 7784535 8018274 63464652 65129292 2580327 1551998 24991458 25940333 9000000 0 674130 676494 37245915 28168825 X 12270789 25140265 13947948 11820202 26218737 36960467 63464652 65129292 X 10128915 502498 110317 X X 0 1 X 1 0 X 48502473 46522410 43451535 43373203 52879488 234729109 48502473 46522410 43451535 43373203 52879488 234729109 91938 234637171 1887633 2074361 1972869 1910285 1987753 9832901 7500 70 4126 11696 244573706 0.95940 0.95400 X SCHEDULE A, PART II, LINE 10, EXPLANATION OF OTHER INCOME: SAVINGS BOND PAYOUT - 2021 AMOUNT: $ 7,500. MISCELLANEOUS - 2023 AMOUNT: $ 70. 2024 AMOUNT: $ 4,126. 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PART X, LINE 2: BRIGHTFOCUS PERFORMED AN EVALUATION OF UNCERTAINTY IN INCOME TAXES FOR THE YEAR ENDED MARCH 31, 2025, AND DETERMINED THAT THERE WERE NO MATTERS THAT WOULD REQUIRE RECOGNITION IN THE CONSOLIDATED FINANCIAL STATEMENTS OR THAT MAY HAVE ANY EFFECT ON ITS TAX-EXEMPT STATUS. PART XII, LINE 4B - OTHER ADJUSTMENTS: CHANGE IN PRESENT VALUE OF GRANTS 4,590. 1 EAST ASIA AND THE PACIFIC 0 0 GRANTMAKING 819000 EUROPE 0 0 GRANTMAKING 2125298 NORTH AMERICA - CANADA AND MEXICO, BUT NOT THE UNITED STATES 0 0 GRANTMAKING 431595 SOUTH AMERICA 0 0 GRANTMAKING 300000 0 0 0 0 0 0 3675893 0 3675893 EAST ASIA & THE PACIFIC MACULAR DEGENERATION RESEARCH BY DAISY YAO SHU, PHD ENTITLED: M2025005N 409500 WIRE TRANSFER 0 EAST ASIA & THE PACIFIC MACULAR DEGENERATION RESEARCH BY MASAYUKI HATA, PHD ENTITLED: M2025006N 409500 WIRE TRANSFER 0 EUROPE (INCLUDING ICELAND & GREENLAND) ALZHEIMER'S DISEASE RESEARCH BY WILLEM ANNAERT, PHD ENTITLED: A2024033S 300000 WIRE TRANSFER 0 EUROPE (INCLUDING ICELAND & GREENLAND) ALZHEIMER'S DISEASE RESEARCH BY FRANCES WISEMAN, PHD ENTITLED: A2024040S 300000 WIRE TRANSFER 0 NORTH AMERICA (WHICH INCLUDES CANADA AND MEXICO, BUT NOT THE U.S.) ALZHEIMER'S DISEASE RESEARCH BY ISABELLE AUBERT, PHD ENTITLED: A2025018S 300000 WIRE TRANSFER 0 SOUTH AMERICA ALZHEIMER'S DISEASE RESEARCH BY CAROLINA OCHOA-ROSALES, PHD ENTITLED: A2025027S 300000 WIRE TRANSFER 0 EUROPE (INCLUDING ICELAND & GREENLAND) ALZHEIMER'S DISEASE RESEARCH BY NADER SAFFARI, PHD ENTITLED: A2025022S 299217 WIRE TRANSFER 0 EUROPE (INCLUDING ICELAND & GREENLAND) ALZHEIMER'S DISEASE RESEARCH BY JOHN HARDY, PHD, FRS ENTITLED: A2025012S 231239 WIRE TRANSFER 0 EUROPE (INCLUDING ICELAND & GREENLAND) ALZHEIMER'S DISEASE RESEARCH BY LAURA FUMAGALLI, PHD ENTITLED: A2025008F 200000 WIRE TRANSFER 0 EUROPE (INCLUDING ICELAND & GREENLAND) ALZHEIMER'S DISEASE RESEARCH BY FEDERICA ANASTASI, PHD ENTITLED: A2025004F 199996 WIRE TRANSFER 0 EUROPE (INCLUDING ICELAND & GREENLAND) MACULAR DEGENERATION RESEARCH BY JOLLE ELISE VERGROESEN, PHD ENTITLED: M2025010F 182000 WIRE TRANSFER 0 EUROPE (INCLUDING ICELAND & GREENLAND) NATIONAL GLAUCOMA RESEARCH BY PETE WILLIAMS, PHD ENTITLED: G2025006S 181181 WIRE TRANSFER 0 EUROPE (INCLUDING ICELAND & GREENLAND) BIRAX RESEARCH FUNDING, ENTITLED: CA2023002 146664 WIRE TRANSFER 0 EUROPE (INCLUDING ICELAND & GREENLAND) ALZHEIMER'S DISEASE RESEARCH BY OLAV M. ANDERSEN, PHD ENTITLED: CA2025001 85000 WIRE TRANSFER 0 NORTH AMERICA (WHICH INCLUDES CANADA AND MEXICO, BUT NOT THE U.S.) ALZHEIMER'S DISEASE RESEARCH BY MALLAR CHAKRAVARTY, PHD ENTITLED: CA2025002 85000 WIRE TRANSFER 0 NORTH AMERICA (WHICH INCLUDES CANADA AND MEXICO, BUT NOT THE U.S.) MIND AND SIGHT DISEASES RESEARCH FUNDING, ENTITLED: CA2023003 46595 WIRE TRANSFER 0 5 11 0 0 0 0 0 0 PART I, LINE 2: BEFORE AN INTERNATIONAL GRANT IS AWARDED OR PAID, BRIGHTFOCUS CONFIRMS THAT THE RECIPIENT AND/OR INSTITUTION SUPPORTING THE RESEARCH IS NOT INCLUDED ON THE OFAC (OFFICE OF FOREIGN ASSETS CONTROL) SANCTIONS LIST OR THE INTERNATIONAL BOYCOTT LIST ON THE FEDERAL REGISTER. AFTER AN INTERNATIONAL GRANT IS AWARDED, BRIGHTFOCUS INTERACTS WITH ALL GRANTEES AT LEAST QUARTERLY BY E-MAIL OR AT SCIENTIFIC MEETINGS. IN ADDITION TO THESE INTERACTIONS, EACH GRANT RECIPIENT IS REQUIRED TO SUBMIT SEPARATE DETAILED ANNUAL SCIENTIFIC PROGRESS AND FINANCIAL REPORTS TO BRIGHTFOCUS. THESE ARE RECEIVED BY THE BRIGHTFOCUS SCIENTIFIC AFFAIRS DEPARTMENT, AND REVIEWED BY SCIENTIFIC STAFF WITH BROAD EXPERTISE, INCLUDING IMAGING, MOLECULAR BIOLOGY AND SIGNALING PATHWAYS, CELL BIOLOGY, ANGIOGENESIS, BIOCHEMISTRY, NEUROSCIENCE, AND GENETICS. SENIOR STAFF REVIEWS EACH PROGRESS REPORT AND EVALUATES THE PROJECT FOR SUFFICIENT PROGRESS TOWARDS THE SPECIFIC AIMS PROPOSED IN THE ORIGINAL APPLICATION OR ANY BUDGETARY CONCERNS. THIS EFFORT IS SUPPORTED BY ADDITIONAL SCIENTIFIC COUNSEL FROM MEMBERS OF THE BRIGHTFOCUS SCIENTIFIC REVIEW COMMITTEES, WHEN REQUIRED. IN ADDITION TO STATEMENTS OF EXPERIMENTAL PROGRESS, ALL GRANTEES ARE ASKED TO REPORT ANY TECHNICAL PUBLICATIONS, MEDIA REPORTS, OR PATENT APPLICATIONS IN WHICH BRIGHTFOCUS-SPONSORED RESEARCH IS DESCRIBED. IF SIGNIFICANT CONCERNS RELATED TO PROGRESS ON THE AWARDS ARE DISCOVERED, AND NOT RESOLVED AFTER INTERACTION WITH THE AWARD GRANTEE, THE BRIGHTFOCUS STAFF RECOMMENDS APPROPRIATE ACTIONS TO THE CHAIR OF THE SCIENTIFIC AFFAIRS COMMITTEE OF THE BOARD OF DIRECTORS. IN ACCORDANCE WITH THE GRANT AGREEMENT TERMS AND CONDITIONS, BRIGHTFOCUS MAY WITHHOLD FUNDING, OR DISCONTINUE AN AWARD, FOR ANY GRANTEE THAT FAILS TO ACHIEVE SUFFICIENT PROGRESS OR SUBMIT REQUIRED REPORTS. AT THE CONCLUSION OF THE GRANT AWARD PERIOD, EACH GRANTEE MUST COMPLETE AND SUBMIT A FINAL REPORT THAT IS ALSO REVIEWED BY THE BRIGHTFOCUS SENIOR SCIENTIFIC STAFF. EVALUATION OF THE WORK OF EACH GRANTEE IS QUALITATIVELY AND QUANTITATIVELY ASSESSED THROUGH VARIOUS METRICS RELATED TO THE IMPACT OF THE GRANT ON ITS TARGETED DISEASE FIELD. SUCH IMPACT METRICS HAVE REVEALED THAT 95% OF BRIGHTFOCUS-SUPPORTED RESEARCH RESULTS IN RESEARCH PUBLICATIONS THAT ADVANCE THE FIELDS SERVED BY BRIGHTFOCUS. THIS IMPACT IS FURTHER SUPPORTED BY ANNUAL CATEGORY NORMALIZED CITATION IMPACT ANALYSIS THAT COMPARES BRIGHTFOCUS-SUPPORTED WORKS TO AN UNBIASED COMPARISON OF IMPACT PERFORMANCE VERSUS THE WORLD AVERAGE. BRIGHTFOCUS-SUPPORTED PUBLICATIONS WERE RECENTLY CITED AT 2 TIMES THE FREQUENCY OF THE WORLD AVERAGE. A FINAL EXAMPLE OF IMPACT ASSESSMENT REVEALED THAT THE SUCCESSES OF BRIGHTFOCUS GRANTEES CONTINUE LONG AFTER THE GRANT EXPIRES. ON AVERAGE, EACH GRANTEE RECEIVES ADDITIONAL GRANTS FOR FOLLOW-ON PROJECTS SPAWNED BY THE BRIGHTFOCUS GRANT, WITH VALUES UP TO 8 TIMES THE LEVEL OF THE INITIAL BRIGHTFOCUS INVESTMENT. BRIGHTFOCUS SOLICITS FEEDBACK FROM ITS GRANTEES AND PROVIDES AN ANONYMOUS FORUM FOR COLLECTING SUCH INFORMATION. THROUGH THE BRIGHTFOCUS FOUNDATION WEBSITE AND WITHIN THE SCIENTIFIC PROGRESS REPORTS, THERE ARE DESIGNATED SECTIONS WHERE AWARDEES ARE ASKED TO PROVIDE FEEDBACK TO THE FOUNDATION. THROUGH THIS MECHANISM, THEY ARE GIVEN THE ABILITY TO ANONYMOUSLY PROVIDE FEEDBACK OR COMMUNICATE THEIR CONCERNS TO PROGRAM STAFF OR THE BRIGHTFOCUS' COMPLIANCE OFFICE. ANY SUGGESTIONS, CONCERNS, COMPLAINTS, OR POSITIVE EXPERIENCES CAN BE OUTLINED AND BROUGHT TO THE ATTENTION OF BRIGHTFOCUS IN THIS MANNER, SO THAT BRIGHTFOCUS CAN ADDRESS ANY AREAS NEEDING IMPROVEMENT, REAFFIRM PRAISE-WORTHY POLICIES, OR OTHERWISE ASSESS NEEDS FOR PROGRAMMATIC CHANGE. THE SENIOR LEADERSHIP PRESENTS AND SUMMARIZES THE STATUS AND PROGRESS ON GRANTS TO THE BRIGHTFOCUS BOARD OF DIRECTORS AT EACH OF THEIR QUARTERLY BOARD MEETINGS. PART I, LINE 3: BRIGHTFOCUS REPORTED THE EXPENDITURES BASED ON THE ACCOUNTING METHOD USED IN ITS AUDITED FINANCIAL STATEMENTS WHICH IS ON AN ACCRUAL BASIS. PART II, LINE 1: BRIGHTFOCUS REPORTED THE EXPENDITURES BASED ON THE ACCOUNTING METHOD USED IN ITS AUDITED FINANCIAL STATEMENTS WHICH IS ON AN ACCRUAL BASIS. PART II, LINE 1, COLUMN (D) REGION: EUROPE (INCLUDING ICELAND & GREENLAND) (D) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY WILLEM ANNAERT, PHD ENTITLED: A2024033S DECODING THE ROLE OF AN ALZHEIMER'S CAUSAL GENE IN DISTINCT BRAIN CELL TYPES. INVESTIGATOR'S SUMMARY: MUTATIONS IN THE GENE ENCODING PRESENILIN2 (PSEN2) CAUSE EARLY ONSET FAMILIAL ALZHEIMER'S DISEASE BUT THUS FAR THIS WAS MAINLY STUDIED IN THE CONTEXT OF A BUILD-UP OF TOXIC AMYLOID AGGREGATES. HOWEVER GIVEN ITS RESTRICTED LOCALIZATION IN DEGRADATIVE COMPARTMENTS, WE HYPOTHESIZE THAT MECHANISMS EXIST LEADING TO DISEASE ONSET THAT MAY DIFFER FROM ITS CLOSE RELATIVE PSEN1. UTILIZING NEW PSEN2 AD MOUSE MODELS AND HUMAN NEURONS/MICROGLIA, WE WILL EMPLOY FUNCTIONAL ASSAYS AND ADVANCED MORPHOLOGICAL STUDIES TO UNRAVEL THE CELL TYPE SPECIFIC CONTRIBUTIONS OF PSEN2 IN AD ETIOPATHOGENESIS. GRANT AWARDED: $300,000, FLEMISH INSTITUTE FOR BIOTECHNOLOGY, GHENT, BELGIUM. REGION: EUROPE (INCLUDING ICELAND & GREENLAND) (D) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY FRANCES WISEMAN, PHD ENTITLED: A2024040S THE ROLE OF DYRK1A KINASE IN ALZHEIMER'S DISEASE MICROGLIA DIFFERENCES. INVESTIGATOR'S SUMMARY: DOWN SYNDROME IS A GENETIC CONDITION, CAUSED BY AN EXTRA COPY OF CHROMOSOME 21, AND IS ASSOCIATED WITH A GREATLY INCREASED RISK OF DEVELOPING EARLY-ONSET DEMENTIA CAUSED BY ALZHEIMER'S DISEASE. RECENT RESEARCH HAS DEMONSTRATED THE BRAIN'S IMMUNE RESPONSE TO ALZHEIMER'S DISEASE PATHOLOGY DIFFERS IN PEOPLE WHO HAVE DOWN SYNDROME AND THAT THIS MAY CONTRIBUTE TO THE DEVELOPMENT OF DEMENTIA. OUR DATA INDICATE THAT THE CHROMOSOME 21 GENE, DYRK1A MAY CONTRIBUTE TO THIS; HERE WE PROPOSE TO TEST THIS HYPOTHESIS IN A NEW CELLULAR MODEL OF ALZHEIMER'S DISEASE IN THE CONTEXT OF TRISOMY OF CHROMOSOME 21. GRANT AWARDED: $300,000, UNIVERSITY COLLEGE LONDON INSTITUTE OF NEUROLOGY, LONDON, UNITED KINGDOM. REGION: EUROPE (INCLUDING ICELAND & GREENLAND) (D) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY FEDERICA ANASTASI, PHD ENTITLED: A2025004F PERSONALIZED PROTEOMICS TO UNDERSTAND AND PREDICT ALZHEIMER'S PROGRESSION. INVESTIGATOR'S SUMMARY: ALZHEIMER'S DISEASE (AD) AFFECTS PEOPLE DIFFERENTLY, LEADING TO VARYING RATES OF MEMORY LOSS AND COGNITIVE DECLINE. WHILE BLOOD TESTS CAN HELP DETECT EARLY SIGNS OF AD, THERE'S STILL MUCH TO LEARN ABOUT WHY THESE DIFFERENCES OCCUR. THIS PROJECT FOCUSES ON IDENTIFYING NEW BIOMARKERS TO EXPLAIN WHY INDIVIDUALS EXPERIENCE AD DIFFERENTLY AND PREDICT WHO WILL BE MOST AFFECTED. BY DISCOVERING THESE MARKERS, WE AIM TO DEVELOP PERSONALIZED TOOLS FOR EARLIER INTERVENTION, IMPROVE PREDICTIONS, AND ENHANCE THE RECRUITMENT OF PARTICIPANTS FOR CLINICAL TRIALS. GRANT AWARDED: $199,996, BARCELONABETA BRAIN RESEARCH CENTER, BARCELONA, SPAIN. REGION: EUROPE (INCLUDING ICELAND & GREENLAND) (D) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY LAURA FUMAGALLI, PHD ENTITLED: A2025008F LEVERAGING HOW THE BRAIN'S IMMUNE CELLS FUEL FRONTOTEMPORAL DEMENTIA. INVESTIGATOR'S SUMMARY: A MUTATION IN THE C9ORF72 GENE IS THE LEADING GENETIC CAUSE OF FTD AND ALS, BUT ITS ROLE IN BRAIN CELL DAMAGE REMAINS UNCLEAR. THE GENE IS HIGHLY ACTIVE IN MICROGLIA, THE BRAIN'S IMMUNE CELLS, WHICH MAY MALFUNCTION DUE TO THIS MUTATION. SINCE UNHEALTHY MICROGLIA CAN WORSEN BRAIN DISEASES, THIS STUDY WILL EXPLORE HOW THE C9ORF72 MUTATION AFFECTS THEM. USING AN INNOVATIVE MODEL THAT MIMICS A BRAIN-LIKE ENVIRONMENT, I WILL ANALYZE HOW THE MUTATION ALTERS MICROGLIAL ACTIVITY AND FUNCTION. THIS RESEARCH COULD REVEAL NOVEL DRUG TARGETS AND DIAGNOSTICS TOOLS. GRANT AWARDED: $200,000, FLANDERS INSTITUTE FOR BIOTECHNOLOGY, ANTWERPEN, BELGIUM. REGION: EUROPE (INCLUDING ICELAND & GREENLAND) (D) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY JOHN HARDY, PHD, FRS ENTITLED: A2025012S A NEW LOOK AT GENETICS USING OLD DATA: ALZHEIMER'S PROGRESSION. INVESTIGATOR'S SUMMARY: WE HAVE SPENT BILLIONS OF DOLLARS AND DECADES STUDYING ALZHEIMER'S DISEASE (AD) BUT HAVE NOT YET FOUND AN EFFECTIVE TREATMENT. MOST ARE BASED ON OUR RESEARCH INTO UNDERSTANDING FACTORS INCREASING THE RISK OF GETTING AD. MODIFICATION OF THOSE FACTORS ARE THEN USED TO SEE IF THE SPEED AT WHICH AD PROGRESSES CAN BE SLOWED DOWN. HOWEVER, THERE IS NO EVIDENCE THAT FACTORS THAT DETERMINE RISK OF GETTING AD ARE THE SAME AS THOSE THAT AFFECT PROGRESSION OF AD! GENETICS CAN TELL US ABOUT BIOLOGY. BY REUSING CLINICAL TRIAL DATA AND THEIR GENETICS, WE CAN SEE WHAT THE BIOLOGY OF PROGRESSION IS. GRANT AWARDED: $231,239, UNIVERSITY COLLEGE LONDON, LONDON, UNITED KINGDOM. REGION: NORTH AMERICA (WHICH INCLUDES CANADA AND MEXICO, BUT NOT THE U.S.) (D) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY ISABELLE AUBERT, PHD ENTITLED: A2025018S USING ULTRASOUND TO HELP THE BRAIN REBUILD MYELIN IN ALZHEIMER'S. INVESTIGATOR'S SUMMARY: ALZHEIMER'S DISEASE AFFECTS BOTH WHITE AND GREY MATTER. THE PREDOMINANT CELLS IN WHITE MATTER, OLIGODENDROCYTES, PRODUCE MYELIN, WHICH INSULATES CELLS TO IMPROVE COMMUNICATION. WHITE MATTER DEFICITS CAN RESULT IN CELL LOSS AND COMMUNICATION BREAKDOWN. IN A PRECLINICAL MODEL OF ALZHEIMER'S DISEASE, WE HAVE DISCOVERED THAT NON-INVASIVE ULTRASOUND WAVES CAN GENERATE NEW OLIGODENDROCYTES THAT MAY BOOST MYELIN PRODUCTION. WITH FUNDING, WE AIM TO DEVELOP THIS INNOVATIVE THERAPY, WHICH HAS THE POTENTIAL TO IMPROVE BRAIN FUNCTION AFFECTED BY ALZHEIMER'S DISEASE, INCLUDING LEARNING AND MEMORY. GRANT AWARDED: $300,000, SUNNYBROOK RESEARCH INSTITUTE, TORONTO, CANADA. REGION: EUROPE (INCLUDING ICELAND & GREENLAND) (D) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY NADER SAFFARI, PHD ENTITLED: A2025022S CAN ULTRASOUND TRIGGER IMMUNE CELLS TO CLEAR TOXINS IN ALZHEIMER'S DISEASE? INVESTIGATOR'S SUMMARY: AS THE POPULATION AGES, ALZHEIMER'S DISEASE CASES ARE INCREASING AND A BUILD-UP IN THE BRAIN OF A HARMFUL PROTEIN, CALLED AMYLOID BETA (A), IS A KEY FACTOR. CURRENT TREATMENTS TO REDUCE A LEVELS ARE COSTLY AND CAN CAUSE SERIOUS SIDE EFFECTS, INCLUDING BRAIN BLEEDING. THIS STUDY EXPLORES ULTRASOUND AS A SAFE, NON-INVASIVE WAY TO HELP BRAIN IMMUNE CELLS, CALLED MICROGLIA, CLEAR THESE PROTEINS: ULTRASOUND ACTIVATES MICROGLIA, RESTORING THEIR ABILITY TO CLEAN THE BRAIN, AND THIS PROMISING METHOD COULD OFFER A MORE EFFECTIVE AND AFFORDABLE TREATMENT FOR ALZHEIMER'S. GRANT AWARDED: $299,217, UNIVERSITY COLLEGE LONDON, LONDON, UNITED KINGDOM. X X X X 1 RKD GROUP 35 PARKWOOD DRIVE STE 160 HOPKINTON MA 01748 FUNDRAISING AND COMMUNICATIONS CONSULTANT 0 33176193 1027076 32149117 33176193 1027076 32149117 AK AL AR AZ CA CO CT DC FL GA HI IL KS KY LA MA MD ME MI MN MO MS NC ND NH NJ NM NV OH OK OR PA RI SC TN UT VA WA WI WV CONCERT FOR CURES 253075 222435 30640 12862 38560 13342 22484 253075 222435 30640 12862 38560 13342 22484 87248 -56608 SCHEDULE G, PART I, LINE 2B, COLUMN (V) IN THE CONTRACT WITH RKD GROUP, THE MANAGEMENT FEES ARE FIXED AMOUNTS PER MONTH FOR IN-SCOPE SERVICES THAT TOTALS $1,243,296 PER YEAR OF WHICH $636,600 HAS BEEN ALLOCATED UNDER PART IX, LINE 11(G) TO PROGRAM AND MANAGEMENT AND ARE NOT CONSIDERED TO BE THE PROFESSIONAL FUNDRAISING CONSULTANT FEE. 1 WILLIAM MARSH RICE UNIVERSITY 6100 MAIN ST BIOSCIENCE RESEARCH COLLABORATIVE HOUSTON TX 77030 741109620 501(C)(3) 409500 0 MACULAR DEGENERATION RESEARCH BY JERZY SZABLOWSKI, PHD ENTITLED: M2025001N UNIVERSITY OF OKLAHOMA HEALTH SCIENCES CENTER 608 STANTON L YOUNG BLVD OKLAHOMA CITY OK 73104 731563627 501(C)(3) 409500 0 MACULAR DEGENERATION RESEARCH BY ANA J CHUCAIR-ELLIOTT, PHD ENTITLED: M2025002N LELAND STANFORD JUNIOR UNIVERSITY BYERS EYE INSTITUTE 2452 WATSON COURT PALO ALTO CA 94303 941156365 501(C)(3) 409500 0 MACULAR DEGENERATION RESEARCH BY CHARLES DEBOER, MD, PHD ENTITLED: M2025004N LELAND STANFORD JUNIOR UNIVERSITY 300 CAMPUS DRIVE GRANT BUILDING OPHTHALMOLOGY DEPT STANFORD CA 94305 941156365 501(C)(3) 409500 0 MACULAR DEGENERATION RESEARCH BY MOHAJEET BALVEER BHUCKORY, PHD ENTITLED: M2025007N NATIONAL EYE INSTITUTE NIH 10 CENTER DRIVE RM 10N116 FLOOR 10 BLD 10 BETHESDA MD 20852 520858115 501(C)(3) 408701 0 MACULAR DEGENERATION RESEARCH BY RUCHI SHARMA, PHD ENTITLED: M2025003N BETH ISRAEL DEACONESS MEDICAL CENTER 330 BROOKLINE AVENUE BOSTON MA 02215 042103881 501(C)(3) 300000 0 ALZHEIMER'S DISEASE RESEARCH BY PETER FRIED, PHD ENTITLED: A2024034S LELAND STANFORD JUNIOR UNIVERSITY 1201 WELCH RD PALO ALTO CA 94305 941156365 501(C)(3) 300000 0 ALZHEIMER'S DISEASE RESEARCH BY AMIRA LATIF HERNANDEZ, PHD ENTITLED: A2024035S UNIVERSITY OF CALIFORNIA SAN DIEGO 9500 GILMAN DRIVE LA JOLLA CA 92093 956006144 501(C)(3) 300000 0 ALZHEIMER'S DISEASE RESEARCH BY JEROME MERTENS, PHD ENTITLED: A2024036S UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE 4333 BROOKLYN AVE NE SEATTLE WA 98195 916001537 501(C)(3) 300000 0 ALZHEIMER'S DISEASE RESEARCH BY JUSTIN MILLER, PHD ENTITLED: A2024037S UNIVERSITY OF CALIFORNIA SAN DIEGO 9500 GILMAN DRIVE LA JOLLA CA 92093 956006144 501(C)(3) 300000 0 ALZHEIMER'S DISEASE RESEARCH BY JOHANNES SCHLACHETZKI, MD ENTITLED: A2024038S UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION 789 S LIMESTONE TODD 565 LEXINGTON KY 40536 616033693 501(C)(3) 300000 0 ALZHEIMER'S DISEASE RESEARCH BY LINDA VAN ELDIK, PHD ENTITLED: A2024039S VANDERBILT UNIVERSITY MEDICAL CENTER 2213 GARLAND AVE NASHVILLE TN 37232 352528741 501(C)(3) 300000 0 ALZHEIMER'S DISEASE RESEARCH BY MONICA SANTISTEBAN, PHD ENTITLED: A2025011S THE J DAVID GLADSTONE INSTITUTES 1650 OWENS ST SAN FRANCISCO CA 94158 237203666 501(C)(3) 300000 0 ALZHEIMER'S DISEASE RESEARCH BY KATERINA AKASSOGLOU, PHD ENTITLED: A2025013S MASSACHUSETTS GENERAL HOSPITAL 114 SIXTEENTH ST CHARLESTOWN MA 02129 042697983 501(C)(3) 300000 0 ALZHEIMER'S DISEASE RESEARCH BY KSENIA KASTANENKA, PHD ENTITLED: A2025014S COLUMBIA UNIVERSITY 622 W 168TH ST NEW YORK NY 10025 135598093 501(C)(3) 300000 0 ALZHEIMER'S DISEASE RESEARCH BY JAE-EUN MILLER, PHD ENTITLED: A2025016S NORTHWESTERN UNIVERSITY - CHICAGO CAMPUS 300 EAST SUPERIOR STREETTARRY 7-758 CHICAGO IL 60611 362167817 501(C)(3) 300000 0 ALZHEIMER'S DISEASE RESEARCH BY JUSTYNA DOBROWOLSKA ZAKARIA, PHD ENTITLED: A2025019S WASHINGTON UNIVERSITY IN STLOUIS CAMPUS BOX 1054 ONE BROOKINGS DRIVE ST LOUIS MO 63130 430653611 501(C)(3) 300000 0 ALZHEIMER'S DISEASE RESEARCH BY CYRIL POTTIER, PHD ENTITLED: A2025020S RESEARCH FOUNDATION OF SUNY - UNIVERSITY AT ALBANY OFFICE FOR SPONSORED PROGRAMS/MSC 312 1400 WASHINGTON AVENUE ALBANY NY 12222 141368361 501(C)(3) 300000 0 ALZHEIMER'S DISEASE RESEARCH BY DAMIAN ZULOAGA, PHD ENTITLED: A2025021S ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI 3 E 101ST ST NEW YORK NY 10029 136171197 501(C)(3) 300000 0 ALZHEIMER'S DISEASE RESEARCH BY JACK HUMPHREY, PHD ENTITLED: A2025024S THE OHIO STATE UNIVERSITY 460 W 12TH AVE COLUMBUS OH 43210 316025986 501(C)(3) 300000 0 ALZHEIMER'S DISEASE RESEARCH BY HONGJUN FU, PHD ENTITLED: A2025025S THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 115 MASON FARM RD 6109C NEUROSCIENCE RESEARCH BUILDING CB 7 CHAPEL HILL NC 27599 566001393 501(C)(3) 300000 0 ALZHEIMER'S DISEASE RESEARCH BY TODD J. COHEN, PHD ENTITLED: A2025026S INDIANA UNIVERSITY 340 WEST 10TH STREET INDIANAPOLIS IN 46202 356001673 501(C)(3) 299843 0 ALZHEIMER'S DISEASE RESEARCH BY MIGUEL MOUTINHO, PHARMD, PHD ENTITLED: A2025015S BETH ISRAEL DEACONESS MEDICAL CENTER 330 BROOKLINE AVENUE BOSTON MA 02115 042103881 501(C)(3) 299838 0 ALZHEIMER'S DISEASE RESEARCH BY FENG TIAN, PHD ENTITLED: A2025017S INDIANA UNIVERSITY NB BUILDING 320 W 15TH ST 414 INDIANAPOLIS IN 46202 356001673 501(C)(3) 297517 0 ALZHEIMER'S DISEASE RESEARCH BY REBECCA WALLINGS, DPHIL ENTITLED: A2025023S MAYO CLINIC JACKSONVILLE 4500 SAN PABLO ROAD JACKSONVILLE FL 32224 593337028 501(C)(3) 235163 0 ALZHEIMER'S DISEASE RESEARCH ENTITLED: CA2021010 EMORY UNIVERSITY 1599 CLIFTON ROAD NE 4TH FLOOR ATLANTA GA 30322 580566256 501(C)(3) 200000 0 ALZHEIMER'S DISEASE RESEARCH BY JOSHNA GADHAVI, PHD ENTITLED: A2024029F UNIVERSITY OF CALIFORNIA SAN FRANCISCO 1550 4TH ST ROCK HALL 381 SAN FRANCISCO CA 94143 946036493 501(C)(3) 200000 0 ALZHEIMER'S DISEASE RESEARCH BY DONG KYU KIM, PHD ENTITLED: A2024030F WASHINGTON UNIVERSITY IN STLOUIS 4370 DUNCAN AVE ST LOUIS MO 63110 430653611 501(C)(3) 200000 0 ALZHEIMER'S DISEASE RESEARCH BY ASHISH SHARMA, PHD ENTITLED: A2024031F COLUMBIA UNIVERSITY 3227 BROADWAY L-5-055 NEW YORK NY 10027 135598093 501(C)(3) 200000 0 ALZHEIMER'S DISEASE RESEARCH BY EMILIANO ZAMPONI, PHD ENTITLED: A2024032F BAYLOR COLLEGE OF MEDICINE ONE BAYLOR PLAZA MS BCM ROOM N930 HOUSTON TX 77030 741613878 501(C)(3) 200000 0 ALZHEIMER'S DISEASE RESEARCH BY OMAR PEA-RAMOS, PHD ENTITLED: A2025002F ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI 1425 MADISON AVENUE FLOOR 9 ROOM 9-02C NEW YORK NY 10029 136171197 501(C)(3) 200000 0 ALZHEIMER'S DISEASE RESEARCH BY MARCOS SCHAAN PROFES, PHD ENTITLED: A2025003F BRIGHAM AND WOMEN'S HOSPITAL INC 60 FENWOOD ROAD BOSTON MA 02115 042312909 501(C)(3) 200000 0 ALZHEIMER'S DISEASE RESEARCH BY SARAH ELISE HEUER, PHD ENTITLED: A2025005F WASHINGTON UNIVERSITY IN STLOUIS 4370 DUNCAN AVE SAINT LOUIS MO 63110 430653611 501(C)(3) 200000 0 ALZHEIMER'S DISEASE RESEARCH BY JOSHUA EMMERSON, PHD ENTITLED: A2025006F UNIVERSITY OF CALIFORNIA IRVINE UNIVERSITY OF CALIFORNIA IRVINE 3014 GROSS HALL IRVINE CA 92697 952226406 501(C)(3) 200000 0 ALZHEIMER'S DISEASE RESEARCH BY GHAZALEH ESKANDARI-SEDIGHI, PHD ENTITLED: A2025007F THE SALK INSTITUTE FOR BIOLOGICAL STUDIES 10010 NORTH TORREY PINES ROAD LA JOLLA CA 92037 952160097 501(C)(3) 200000 0 ALZHEIMER'S DISEASE RESEARCH BY JOSEPH HERDY, PHD ENTITLED: A2025010F UNIVERSITY OF PITTSBURGH BIOMEDICAL SCIENCE TOWER 3 3501 FIFTH AVENUE PITTSBURGH PA 15213 250965591 501(C)(3) 199724 0 ALZHEIMER'S DISEASE RESEARCH BY JR-JIUN LIOU, PHD ENTITLED: A2025009F MAYO CLINC ROCHESTER 200 FIRST ST SW ROCHESTER MN 55905 416011702 501(C)(3) 182000 0 NATIONAL GLAUCOMA RESEARCH BY GAVIN RODDY, MD, PHD ENTITLED: G2025001S UNIVERSITY OF CALIFORNIA SAN DIEGO 9452 MEDICAL CENTER DRIVE LA JOLLA CA 92037 956006144 501(C)(3) 182000 0 NATIONAL GLAUCOMA RESEARCH BY KARL JONAS WAHLIN, PHD ENTITLED: G2025002S UNIVERSITY OF WISCONSIN-MADISON DEPARTMENT OF OPHTHALMOLOGY MADISON WI 53706 396006492 501(C)(3) 182000 0 NATIONAL GLAUCOMA RESEARCH BY ROB NICKELLS, PHD ENTITLED: G2025003S DUKE UNIVERSITY SCHOOL OF MEDICINE 2200 W MAIN STREET SUITE 710 DURHAM NC 27705 560532129 501(C)(3) 182000 0 NATIONAL GLAUCOMA RESEARCH BY DAN STAMER, PHD ENTITLED: G2025004S UNIVERSITY OF SOUTHERN CALIFORNIA DEPARTMENT OF OPHTHALMOLOGY 1450 SAN PABLO STREET 4TH FLOOR LOS ANGELES CA 90033 951642394 501(C)(3) 182000 0 NATIONAL GLAUCOMA RESEARCH BY BENJAMIN XU, MD, PHD ENTITLED: G2025005S THE SCHEPENS EYE RESEARCH INSTITUTE INC 20 STANIFORD STREET BOSTON MA 02114 042129889 501(C)(3) 182000 0 NATIONAL GLAUCOMA RESEARCH BY TATJANA JAKOBS, MD ENTITLED: G2025008S UNIVERSITY OF CALIFORNIA IRVINE 324 ALDRICH HALL IRVINE CA 92697 952226406 501(C)(3) 182000 0 NATIONAL GLAUCOMA RESEARCH BY DOROTA SKOWRONSKA-KRAWCZYK, PHD ENTITLED: G2025009S UNIVERSITY OF WISCONSIN-MADISON DEPARTMENT OF OPHTHALMOLOGY VISUAL SCIENCES 3375 MEDICAL SCIENCES CENT MADISON WI 53706 396006492 501(C)(3) 182000 0 NATIONAL GLAUCOMA RESEARCH BY COLLEEN MCDOWELL, PHD ENTITLED: G2025010S UNIVERSITY OF CALIFORNIA SAN FRANCISCO 1550 4TH STREET ROOM 445 SAN FRANCISCO CA 94158 946036493 501(C)(3) 182000 0 MACULAR DEGENERATION RESEARCH BY VALENCIA FERNANDES, PHD ENTITLED: M2025008F DUKE UNIVERSITY SCHOOL OF MEDICINE 2351 ERWIN RD AERI 3000 DURHAM NC 27705 560532129 501(C)(3) 182000 0 MACULAR DEGENERATION RESEARCH BY DR. NOBUHIKO SHIRAKI, PHD ENTITLED: M2025011F UNIVERSITY OF CALIFORNIA SAN DIEGO 9500 GILMAN DRIVE LA JOLLA CA 92093 956006144 501(C)(3) 182000 0 MACULAR DEGENERATION RESEARCH BY JAESOO JUNG, PHD ENTITLED: M20250013F GOOD SAMARITAN FOUNDATION 1225 NE 2ND AVENUE 3RD FLOOR PORTLAND OR 97232 237017276 501(C)(3) 181798 0 NATIONAL GLAUCOMA RESEARCH BY BRAD FORTUNE, OD, PHD ENTITLED: G2025007S UNIVERSITY OF IDAHO 875 PERIMETER DRIVE MS 3020 MOSCOW ID 83844 826000945 501(C)(3) 180864 0 MACULAR DEGENERATION RESEARCH BY ASHLEY FARRE, PHD ENTITLED: M2025012F INDIANA UNIVERSITY 635 BARNHILL DRIVE INDIANAPOLIS IN 46202 356001673 501(C)(3) 180523 0 ALZHEIMER'S DISEASE RESEARCH BY ANLLELY FERNANDEZ, PHD ENTITLED: A2025001F THE FISHER CENTER FOR ALZHEIMERS DISEASE RESEARCH FDR STATION PO BOX 220 NEW YORK NY 10150 133859563 501(C)(3) 133597 0 ALZHEIMER'S DISEASE RESEARCH FUNDING INTERNATIONAL SOCIETY FOR MOLECULAR NEURODEGENERATION 1001 MAYPORT ROAD PO BOX 331076 ATLANTIC BEACH FL 32233 862907045 501(C)(3) 115000 0 ALZHEIMER'S DISEASE RESEARCH ENTITLED: CA2021011 MEDICAL TECHNOLOGY ENTERPRISE CONSORTIUM 315 SIGMA DRIVE SUMMERVILLE SC 29486 474960128 501(C)(3) 100000 0 ALZHEIMER'S DISEASE RESEARCH ENTITLED: CA2025003 JOHNS HOPKINS UNIVERSITY 3910 KESWICK ROAD N4327B BALTIMORE MD 21211 520595110 501(C)(3) 75000 0 RRESTORE CONSORTIUM RESEARCH FUNDING AND TRAVEL GRANTS FOR CONFERENCE ATTENDEES HELEN KELLER FOUNDATION FOR RESEARCH & EDUCATION 1201 11TH AVE SOUTH SUITE 300 BIRMINGHAM AL 35205 630983733 501(C)(3) 75000 0 HELEN KELLER PRIZE FOR VISION RESEARCH FUNDING INTERNATIONAL SOCIETY FOR EYE RESEARCH 655 BEACH STREET SAN FRANCISCO CA 94109 510171667 501(C)(3) 30000 0 TRAVEL GRANTS FOR CONFERENCE ATTENDEES AND RESEARCH SPONSORSHIP ARVO FOUNDATION FOR EYE RESEARCH 1801 ROCKVILLE PIKE SUITE 400 ROCKVILLE MD 20852 522322462 501(C)(3) 15240 0 TRAVEL GRANTS FOR CONFERENCE ATTENDEES 57 0 PART I, LINE 2: AFTER AN INTERNATIONAL GRANT IS AWARDED, BRIGHTFOCUS INTERACTS WITH ALL GRANTEES AT LEAST QUARTERLY BY E-MAIL OR AT SCIENTIFIC MEETINGS. IN ADDITION TO THESE INTERACTIONS, EACH GRANT RECIPIENT IS REQUIRED TO SUBMIT SEPARATE DETAILED ANNUAL SCIENTIFIC PROGRESS AND FINANCIAL REPORTS TO BRIGHTFOCUS. THESE ARE RECEIVED BY THE BRIGHTFOCUS SCIENTIFIC AFFAIRS DEPARTMENT, AND REVIEWED BY SCIENTIFIC STAFF WITH BROAD EXPERTISE, INCLUDING IMAGING, MOLECULAR BIOLOGY AND SIGNALING PATHWAYS, CELL BIOLOGY, ANGIOGENESIS, BIOCHEMISTRY, NEUROSCIENCE, AND GENETICS. SENIOR STAFF REVIEWS EACH PROGRESS REPORT AND EVALUATES THE PROJECT FOR SUFFICIENT PROGRESS TOWARDS THE SPECIFIC AIMS PROPOSED IN THE ORIGINAL APPLICATION OR ANY BUDGETARY CONCERNS. THIS EFFORT IS SUPPORTED BY ADDITIONAL SCIENTIFIC COUNSEL FROM MEMBERS OF THE BRIGHTFOCUS SCIENTIFIC REVIEW COMMITTEES, WHEN REQUIRED. IN ADDITION TO STATEMENTS OF EXPERIMENTAL PROGRESS, ALL GRANTEES ARE ASKED TO REPORT ANY TECHNICAL PUBLICATIONS, MEDIA REPORTS, OR PATENT APPLICATIONS IN WHICH BRIGHTFOCUS-SPONSORED RESEARCH IS DESCRIBED. IF SIGNIFICANT CONCERNS RELATED TO PROGRESS ON THE AWARDS ARE DISCOVERED, AND NOT RESOLVED AFTER INTERACTION WITH THE AWARD GRANTEE, THE BRIGHTFOCUS STAFF RECOMMENDS APPROPRIATE ACTIONS TO THE CHAIR OF THE SCIENTIFIC AFFAIRS COMMITTEE OF THE BOARD OF DIRECTORS. IN ACCORDANCE WITH THE GRANT AGREEMENT TERMS AND CONDITIONS, BRIGHTFOCUS MAY WITHHOLD FUNDING, OR DISCONTINUE AN AWARD, FOR ANY GRANTEE THAT FAILS TO ACHIEVE SUFFICIENT PROGRESS OR SUBMIT REQUIRED REPORTS. AT THE CONCLUSION OF THE GRANT AWARD PERIOD, EACH GRANTEE MUST COMPLETE AND SUBMIT A FINAL REPORT THAT IS ALSO REVIEWED BY THE BRIGHTFOCUS SENIOR SCIENTIFIC STAFF. EVALUATION OF THE WORK OF EACH GRANTEE IS QUALITATIVELY AND QUANTITATIVELY ASSESSED THROUGH VARIOUS METRICS RELATED TO THE IMPACT OF THE GRANT ON ITS TARGETED DISEASE FIELD. SUCH IMPACT METRICS HAVE REVEALED THAT 95% OF BRIGHTFOCUS-SUPPORTED RESEARCH RESULTS IN RESEARCH PUBLICATIONS THAT ADVANCE THE FIELDS SERVED BY BRIGHTFOCUS. THIS IMPACT IS FURTHER SUPPORTED BY ANNUAL CATEGORY NORMALIZED CITATION IMPACT ANALYSIS THAT COMPARES BRIGHTFOCUS-SUPPORTED WORKS TO AN UNBIASED COMPARISON OF IMPACT PERFORMANCE VERSUS THE WORLD AVERAGE. BRIGHTFOCUS-SUPPORTED PUBLICATIONS WERE RECENTLY CITED AT 2 TIMES THE FREQUENCY OF THE WORLD AVERAGE. A FINAL EXAMPLE OF IMPACT ASSESSMENT REVEALED THAT THE SUCCESSES OF BRIGHTFOCUS GRANTEES CONTINUE LONG AFTER THE GRANT EXPIRES. ON AVERAGE, EACH GRANTEE RECEIVES ADDITIONAL GRANTS FOR FOLLOW-ON PROJECTS SPAWNED BY THE BRIGHTFOCUS GRANT, WITH VALUES UP TO 8 TIMES THE LEVEL OF THE INITIAL BRIGHTFOCUS INVESTMENT. BRIGHTFOCUS SOLICITS FEEDBACK FROM ITS GRANTEES AND PROVIDES AN ANONYMOUS FORUM FOR COLLECTING SUCH INFORMATION. THROUGH THE BRIGHTFOCUS FOUNDATION WEBSITE AND WITHIN THE SCIENTIFIC PROGRESS REPORTS, THERE ARE DESIGNATED SECTIONS WHERE AWARDEES ARE ASKED TO PROVIDE FEEDBACK TO THE FOUNDATION. THROUGH THIS MECHANISM, THEY ARE GIVEN THE ABILITY TO ANONYMOUSLY PROVIDE FEEDBACK OR COMMUNICATE THEIR CONCERNS TO PROGRAM STAFF OR THE BRIGHTFOCUS' COMPLIANCE OFFICE. ANY SUGGESTIONS, CONCERNS, COMPLAINTS, OR POSITIVE EXPERIENCES CAN BE OUTLINED AND BROUGHT TO THE ATTENTION OF BRIGHTFOCUS IN THIS MANNER, SO THAT BRIGHTFOCUS CAN ADDRESS ANY AREAS NEEDING IMPROVEMENT, REAFFIRM PRAISE-WORTHY POLICIES, OR OTHERWISE ASSESS NEEDS FOR PROGRAMMATIC CHANGE. THE SENIOR LEADERSHIP PRESENTS AND SUMMARIZES THE STATUS AND PROGRESS ON GRANTS TO THE BRIGHTFOCUS BOARD OF DIRECTORS AT EACH OF THEIR QUARTERLY BOARD MEETINGS. PART II, LINE 1(H) NAME OF ORGANIZATION OR GOVERNMENT: EMORY UNIVERSITY (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY JOSHNA GADHAVI, PHD ENTITLED: A2024029F ASSESSING THE IMPACT OF BLOOD-BRAIN BARRIER DYSFUNCTION IN ALZHEIMER'S DISEASE. INVESTIGATOR'S SUMMARY: BLOOD-BRAIN BARRIER (BBB) BREAKDOWN HAS BEEN OBSERVED IN VARIOUS NEURODEGENERATIVE DISEASES INCLUDING ALZHEIMER'S DISEASE. IN A HEALTHY BRAIN, THE BBB DOES NOT ALLOW TRANSPORTATION OF PROTEINS OR LARGE MOLECULES INTO THE BRAIN. HOWEVER, DUE TO BBB DYSFUNCTION, ENHANCED PERMEABILITY OF PLASMA-DERIVED PROTEINS CAN BE OBSERVED IN DIFFERENT PARTS OF BRAIN REGIONS, AND MAY LEAD TO NEUROTOXICITY, NEUROINFLAMMATION, AND OXIDATIVE STRESS. THIS PROJECT WILL IDENTIFY NOVEL BIOMARKERS AND KEY TARGETS FOR BBB BREAKDOWN AND EXPLORE HOW IT MAY CONTRIBUTE TO ALZHEIMER'S DIAGNOSIS AND PROGRESSION. NAME OF ORGANIZATION OR GOVERNMENT: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY DONG KYU KIM, PHD ENTITLED: A2024030F DEFINING THE IMPACT OF CYTOKINE SIGNALING IN ALZHEIMER'S DISEASE. INVESTIGATOR'S SUMMARY: IMMUNE SIGNALS REGULATE BRAIN HOMEOSTASIS AND ARE ALSO A MAJOR DRIVER OF ALZHEIMER'S DISEASE PATHOLOGY. THIS STUDY WILL INVESTIGATE HOW ASTROCYTE-MICROGLIA CROSSTALK VIA IL-33 CYTOKINE IMPACTS ALZHEIMER'S DISEASE PATHOLOGY AND BEHAVIOR. THIS WORK WILL DETERMINE THE MECHANISTIC IMPACT OF A KEY IMMUNE PATHWAY IN AD PATHOLOGY AND SUGGEST THE NOVEL HYPOTHESIS THAT ECM DISRUPTION IS LINKED TO AD PATHOLOGY. NAME OF ORGANIZATION OR GOVERNMENT: WASHINGTON UNIVERSITY IN ST. LOUIS (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY ASHISH SHARMA, PHD ENTITLED: A2024031F CIRCADIAN RHYTHM DISRUPTION AND ALZHEIMER'S DISEASE. INVESTIGATOR'S SUMMARY: THIS STUDY INVESTIGATES HOW DISRUPTIONS TO CIRCADIAN RHYTHMS, COMMON IN AGING AND ALZHEIMER'S DISEASE, IMPACT DISEASE PROGRESSION USING A MOUSE MODEL OF CHRONIC JETLAG (CJL). RESEARCHERS AIM TO UNDERSTAND HOW CJL AFFECTS ALZHEIMER'S MARKERSAMYLOID PLAQUES AND TAU PROTEIN ACCUMULATION. INVESTIGATING THE CONNECTION BETWEEN CIRCADIAN DISRUPTION, GLIAL FUNCTION, AND ALZHEIMER'S-RELATED CHANGES MAY REVEAL THERAPEUTIC STRATEGIES, OFFERING NOVEL APPROACHES TO DISEASE PREVENTION. NAME OF ORGANIZATION OR GOVERNMENT: COLUMBIA UNIVERSITY (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY EMILIANO ZAMPONI, PHD ENTITLED: A2024032F MECHANISMS OF INHIBITORY NEURON VULNERABILITY TO ALZHEIMER'S DISEASE. INVESTIGATOR'S SUMMARY: INHIBITORY INTERNEURONS, ONE OF THE KEY PLAYERS IN HUMAN COGNITIVE PROCESSES, ARE AMONG THE FIRST NEURONAL POPULATIONS AFFECTED BY AD ONSET. I PROPOSE THEIR ELEVATED ENERGY CONSUMPTION RATES MAKE THESE INTERNEURONS MORE VULNERABLE TO AD. USING MULTIPLE INNOVATIVE APPROACHES, I WILL INVESTIGATE THREE FUNDAMENTAL ASPECTS UNDERLYING INHIBITORY INTERNEURON VULNERABILITY TO AD. BY COMPLETING THE AIMS OF MY PROPOSAL, I EXPECT TO GAIN NEW INSIGHTS INTO THE PATHOLOGICAL BASIS OF THIS SOCIALLY DEVASTATING NEUROLOGICAL CONDITION AND TO DEVELOP NOVEL THERAPEUTIC APPROACHES. NAME OF ORGANIZATION OR GOVERNMENT: BETH ISRAEL DEACONESS MEDICAL CENTER (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY PETER FRIED, PHD ENTITLED: A2024034S TREATING INSOMNIA IN MILD COGNITIVE IMPAIRMENT. INVESTIGATOR'S SUMMARY: MANY PEOPLE WITH MILD COGNITIVE IMPAIRMENT (MCI) EXPERIENCE SYMPTOMS OF INSOMNIA, SUCH AS DIFFICULTY FALLING OR STAYING ASLEEP, WHICH CAN SPEED COGNITIVE DECLINE AND WORSEN QUALITY OF LIFE. WE PROPOSE TO TEST A NOVEL INTERVENTION TO IMPROVE SLEEP AND COGNITION IN PERSONS WITH MCI THAT COMBINES NONINVASIVE NEUROMODULATION WITH TRANSCRANIAL MAGNETIC STIMULATION WITH AN INTERNET-DELIVERED COGNITIVE BEHAVIORAL THERAPY FOR INSOMNIA PROGRAM. IF SUCCESSFUL, THIS APPROACH WILL MEET THE NEED FOR AN EFFICACIOUS, NON-PHARMACOLOGIC, AND ACCESSIBLE THERAPY FOR PERSONS WITH MCI AND INSOMNIA. NAME OF ORGANIZATION OR GOVERNMENT: LELAND STANFORD JUNIOR UNIVERSITY (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY AMIRA LATIF HERNANDEZ, PHD ENTITLED: A2024035S TARGETING BRAIN CELL MISCOMMUNICATION TO RESTORE MEMORY IN ALZHEIMER'S DISEASE. INVESTIGATOR'S SUMMARY: THE BRAIN'S ABILITY TO ADAPT AND CHANGE, KNOWN AS SYNAPTIC PLASTICITY, REQUIRES THE EXPRESSION OF SPECIFIC GENES AND PROTEINS IN DIFFERENT BRAIN CELLS, NEURONS AND ASTROCYTES, WHICH IS AFFECTED IN BRAIN DISORDERS LIKE ALZHEIMER'S. IN ORDER TO FIND POTENTIAL THERAPEUTIC STRATEGIES TO RECOVER SYNAPTIC PLASTICITY, CELL COMMUNICATION, AND TO IMPROVE MEMORY IN ALZHEIMER'S, WE WILL USE ADVANCED TECHNIQUES IN MOUSE MODELS AND LAB-GROWN HUMAN CELLS WITH ALZHEIMER'S-LIKE PATHOLOGY. OUR RESULTS WILL CONTRIBUTE TO THE DEVELOPMENT OF IMPROVED TREATMENTS FOR PATIENTS WITH SYNAPTIC PLASTICITY DISORDERS. NAME OF ORGANIZATION OR GOVERNMENT: UNIVERSITY OF CALIFORNIA, SAN DIEGO (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY JEROME MERTENS, PHD ENTITLED: A2024036S CANCER-LIKE METABOLIC CHANGES IN ALZHEIMER'S DISEASE NEURONS. INVESTIGATOR'S SUMMARY: THIS RESEARCH FOCUSES ON HOW METABOLIC CHANGES IMPACT GENE EXPRESSION AND PROTEIN MODIFICATIONS IN ALZHEIMER'S DISEASE (AD). USING NEURONS FROM AD PATIENTS, WE'VE IDENTIFIED DISRUPTIONS IN METABOLIC PATHWAYS LEADING TO ABNORMAL GENE PROCESSING. OUR STUDY AIMS TO UNDERSTAND HOW THESE CHANGES CONTRIBUTE TO KEY AD FEATURES, SUCH AS TAU TANGLE FORMATION. BY UNDERSTANDING UPSTREAM METABOLIC PATHWAYS OF AD PATHOLOGY, WE AIM TO IDENTIFY POTENTIAL INTERVENTION TARGETS TO RESCUE THE LOSS OF SYNAPTIC FUNCTION AND PREVENT NEURONAL CELL DEATH. NAME OF ORGANIZATION OR GOVERNMENT: UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY JUSTIN MILLER, PHD ENTITLED: A2024037S EXPLORING RURAL HEALTH DISPARITIES IN ALZHEIMER'S DISEASE. INVESTIGATOR'S SUMMARY: THERE IS EMERGING EVIDENCE THAT OLDER ADULTS LIVING IN RURAL COMMUNITIES ARE AT INCREASED RISK FOR ALZHEIMER'S DISEASE (AD); HOWEVER, RURAL COMMUNITIES HAVE BEEN SEVERELY UNDERREPRESENTED IN AD RESEARCH, AND THE FACTORS THAT MAY BE CONTRIBUTING TO THESE URBAN-RURAL DISPARITIES ARE UNCLEAR. OUR LONG-TERM GOAL IS TO FULLY CHARACTERIZE COGNITIVE AGING AND VALIDATE AD-SPECIFIC BIOMARKERS AMONG RURAL-DWELLING OLDER ADULTS. THIS PROJECT WILL ENRICH THE BIOMARKER CHARACTERIZATION OF OUR RURAL COHORT AND FACILITATE IDENTIFICATION OF THE MOST VIABLE BLOOD MARKERS FOR USE IN RURAL-DWELLING OLDER ADULTS. PART II, LINE 1(H) CONTINUED NAME OF ORGANIZATION OR GOVERNMENT: UNIVERSITY OF CALIFORNIA, SAN DIEGO (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY JOHANNES SCHLACHETZKI, MD ENTITLED: A2024038S REGULATION OF MICROGLIA PHENOTYPES IN ALZHEIMER'S DISEASE. INVESTIGATOR'S SUMMARY: ALZHEIMER'S DISEASE IS DEFINED BY THE ACCUMULATION OF HARMFUL PROTEINS IN THE BRAIN. MICROGLIA, THE IMMUNE CELLS OF THE BRAIN, PLAY A KEY ROLE IN THIS PROCESS, BUT THE MOLECULAR MECHANISMS THAT LEAD TO DISTINCT PHENOTYPES ARE UNCLEAR. THIS STUDY WILL USE ADVANCED TECHNIQUES TO ISOLATE AND ANALYZE MICROGLIA, REVEALING HOW THEY CONTRIBUTE TO DISEASE AND IDENTIFYING NEW TARGETS FOR DEVELOPING EFFECTIVE TREATMENTS. WE WILL TEST THE HYPOTHESIS THAT SPECIFIC GROUPS OF PROTEIN FAMILIES (MIT/TFE AND AP-1), ARE RESPONSIBLE FOR CONTROLLING THE GENES THAT MICROGLIA TURN ON OR OFF IN ALZHEIMER'S DISEASE. NAME OF ORGANIZATION OR GOVERNMENT: UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY LINDA VAN ELDIK, PHD ENTITLED: A2024039S DYSREGULATED ASTROCYTE P38, BRAIN INFLAMMATION, AND ALZHEIMER'S PATHOLOGY. INVESTIGATOR'S SUMMARY: ASTROCYTES, THE MOST ABUNDANT GLIAL CELL TYPE IN THE BRAIN, BECOME ABNORMALLY ACTIVATED EARLY IN ALZHEIMER'S DISEASE (AD) AND CAN LEAD TO DETRIMENTAL BRAIN INFLAMMATION AND NERVE CELL DAMAGE. THE P38 MAPK DRIVES INFLAMMATION IN MICROGLIA BUT ITS ROLE IN ASTROCYTES IS UNDERSTUDIED. OUR PROJECT WILL USE NOVEL MOUSE MODELS AND WELL-CHARACTERIZED HUMAN BIOSPECIMENS TO DEFINE THE POTENTIAL LINKAGE BETWEEN ASTROCYTE P38, NEUROINFLAMMATION, AND AD NEUROPATHOLOGIC CHANGE, THUS PROVIDING NEW INSIGHT INTO MECHANISMS BY WHICH ABNORMAL ASTROCYTE ACTIVATION IN AD CONTRIBUTES TO DISEASE PROGRESSION. NAME OF ORGANIZATION OR GOVERNMENT: INDIANA UNIVERSITY (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY ANLLELY FERNANDEZ, PHD ENTITLED: A2025001F LINKING PLAQUE SHAPES TO AMYLOID STRUCTURES IN ALZHEIMER DISEASE. INVESTIGATOR'S SUMMARY: ALZHEIMER DISEASE (AD) IS MARKED BY ABNORMAL DEPOSITS OF AMYLOID- (A) AND TAU PROTEINS IN THE BRAIN, LEADING TO MEMORY LOSS AND COGNITIVE DECLINE. USING CUTTING-EDGE CRYO-ELECTRON MICROSCOPY, WE AIM TO STUDY THE STRUCTURES OF A IN DIFFERENT PLAQUE TYPES AND BRAIN REGIONS. OUR RESEARCH FOCUSES ON UNDERSTANDING HOW THESE STRUCTURAL VARIATIONS CONTRIBUTE TO DISEASE PROGRESSION, ESPECIALLY IN CASES LINKED TO GENETIC RISK FACTORS LIKE APOEE4. THIS WORK COULD UNCOVER NEW DIAGNOSTIC MARKERS AND THERAPEUTIC TARGETS, ADVANCING EFFORTS TO COMBAT AD AND RELATED DISORDERS. NAME OF ORGANIZATION OR GOVERNMENT: BAYLOR COLLEGE OF MEDICINE (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY OMAR PEA-RAMOS, PHD ENTITLED: A2025002F THE ASTROCYTE CELL SURFACE PROTEOME IN ALZHEIMER'S DISEASE. INVESTIGATOR'S SUMMARY: CELL SURFACE PROTEINS (CSPS) HELP CELLS COMMUNICATE AND RESPOND TO THEIR ENVIRONMENT, MAKING THEM KEY DRUG TARGETS. WE PERFORMED CSP PROFILING OF MOUSE ASTROCYTES DURING A-AMYLOID PLAQUE BUILDUP AND IDENTIFIED CD44 AS A TOP CANDIDATE. WE FOUND THAT WHEN CD44 BINDS TO ITS LIGAND OPN, ASTROCYTES TRIGGER LIPID ACCUMULATION WHILE MICE LACKING CD44 SHOW REDUCED INFLAMMATION. BY STUDYING CD44 IN LIVE MICE AND CULTURED ASTROCYTES, WE AIM TO UNCOVER ITS ROLE IN AD AND EXPLORE ITS POTENTIAL AS A THERAPEUTIC TARGET. NAME OF ORGANIZATION OR GOVERNMENT: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY MARCOS SCHAAN PROFES, PHD ENTITLED: A2025003F THE ROLE OF JADE1 IN TAUOPATHY. INVESTIGATOR'S SUMMARY: TAUOPATHIES, SUCH AS ALZHEIMER'S DISEASE, RESULT FROM THE TOXIC AGGREGATION OF TAU PROTEINS, BUT THE EXACT PROCESS REMAINS UNCLEAR. WE ARE INVESTIGATING JADE1, A PROTEIN THAT SPECIFICALLY BINDS TOXIC TAU, TO DETERMINE IF IT PREVENTS AGGREGATION OR PROMOTES CLEARANCE VIA CELLULAR PATHWAYS LIKE AUTOPHAGY. USING ADVANCED CELLULAR MODELS, INCLUDING ONE THAT USES LIGHT TO CONTROL TAU BEHAVIOR, OUR RESEARCH AIMS TO UNCOVER HOW JADE1 WORKS AND EXPLORE ITS POTENTIAL AS A TARGET FOR FUTURE TREATMENTS. NAME OF ORGANIZATION OR GOVERNMENT: BRIGHAM AND WOMEN'S HOSPITAL, INC. (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY SARAH ELISE HEUER, PHD ENTITLED: A2025005F DETERMINING THE CELLULAR IMPACTS OF ABCA7 MUTATIONS IN ALZHEIMER'S DISEASE. INVESTIGATOR'S SUMMARY: GENETICS PLAYS A KEY ROLE IN GOVERNING ALZHEIMER'S DISEASE (AD) RISK, WITH MANY MUTATIONS LINKED TO LIPID BIOLOGY PROTEINS. ABCA7 IS A LIPID TRANSPORTER AND HAS SEVERAL AD RISK MUTATIONS, SOME FOUND EXCLUSIVELY IN INDIVIDUALS OF AFRICAN ANCESTRY. HOWEVER, THE EFFECTS OF THESE MUTATIONS REMAIN UNCLEAR DUE TO THE HISTORICAL LACK OF DIVERSE REPRESENTATION IN RESEARCH STUDIES. USING MODELS OF LIVING BRAIN CELLS DERIVED FROM HUMANS THAT HARBOR THESE MUTATIONS, I WILL STUDY HOW MODIFYING ABCA7 ALTERS PROTEINS, LIPIDS, AND CELL FUNCTION, PAVING THE WAY FOR INCLUSIVE, PERSONALIZED AD THERAPIES. NAME OF ORGANIZATION OR GOVERNMENT: WASHINGTON UNIVERSITY IN ST. LOUIS (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY JOSHUA EMMERSON, PHD ENTITLED: A2025006F TARGETING THE ADAPTIVE IMMUNITY TO PREVENT ALZHEIMER'S BRAIN DEGENERATION. INVESTIGATOR'S SUMMARY: NEURODEGENERATIVE DISEASES SUCH AS ALZHEIMER'S DISEASE (AD) INVOLVE THE BUILDUP OF TAU PROTEINS AND SIGNIFICANT BRAIN DEGENERATION. THIS TAU-MEDIATED DAMAGE IS MAINLY DRIVEN BY INFLAMMATION IN THE BRAIN, WITH RECENT EVIDENCE OF INFILTRATING T-LYMPHOCYTES (T-CELLS) BEING ESSENTIAL TO THIS PROCESS. THIS PROJECT WILL APPLY MULTIDISCIPLINARY APPROACHES TO DETERMINE THE CANDIDATE SIGNALING PATHWAY(S) RESPONSIBLE FOR ATTRACTING T-CELLS TO THE BRAIN IN DISEASE, AND TO BLOCK T-CELL INFILTRATION AS TO PREVENT SUBSEQUENT TAU-MEDIATED BRAIN DEGENERATION IN A GENETICALLY MODIFIED MOUSE MODEL. NAME OF ORGANIZATION OR GOVERNMENT: UNIVERSITY OF CALIFORNIA, IRVINE (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY GHAZALEH ESKANDARI-SEDIGHI, PHD ENTITLED: A2025007F UNDERSTANDING THE ROLE OF BRAIN IMMUNE CELLS IN PROTECTION AGAINST ALZHEIMER'S. INVESTIGATOR'S SUMMARY: UNDERSTANDING HOW ALZHEIMER'S DISEASE (AD) IS FORMED IS CHALLENGING DUE TO THE COMPLEX, MULTIFACETED NATURE OF THE DISEASE. IT IS KNOWN NOW THAT THE HERITABILITY OF AD IS OVER 60%. SO, UNDERSTANDING THE DISEASE MECHANISM, CAN BE ACHIEVED BY EXPLORING THESE HEREDITARY ELEMENTS IN PATIENTS VS. HEALTHY INDIVIDUALS. OF NOTE, SOME RARE HEREDITARY FACTORS TURN OUT TO BE PROTECTIVE AND CAN PROVIDE PROTECTION AGAINST AD. TAKING ADVANTAGE OF NOVEL, MULTI-FACETED STEM CELL MODELS, WE WILL STUDY APOE3 CHRISTCHURCH AS ONE OF SUCH RARE, RESILIENT FACTORS, WITH SPECIFIC FOCUS ON BRAIN RESIDENT IMMUNE CELLS. PART II, LINE 1(H) CONTINUED NAME OF ORGANIZATION OR GOVERNMENT: UNIVERSITY OF PITTSBURGH (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY JR-JIUN LIOU, PHD ENTITLED: A2025009F NEUROIMAGING AND NEUROPATHOLOGY OF ALZHEIMER'S DISEASE IN DOWN SYNDROME. INVESTIGATOR'S SUMMARY: WHY DO INDIVIDUALS WITH DOWN SYNDROME DEVELOP ALZHEIMER'S DISEASE DECADES EARLIER THAN THE GENERAL POPULATION? THIS PROPOSAL WILL USE HIGH-RESOLUTION IMAGING AND POSTMORTEM BRAIN SAMPLES FROM WELL-CHARACTERIZED COHORTS OF ADULTS WITH DOWN SYNDROME AND LATE-ONSET ALZHEIMER'S DISEASE. BY IDENTIFYING IMAGING BIOMARKERS AND CLARIFYING EARLY DISEASE MECHANISMS, WE AIM TO ADVANCE UNDERSTANDING OF ALZHEIMER'S IN DOWN SYNDROME, PROMOTE INCLUSIVE RESEARCH, AND GUIDE EFFECTIVE INTERVENTIONS TO IMPROVE DIAGNOSTICS AND TREATMENT STRATEGIES. NAME OF ORGANIZATION OR GOVERNMENT: THE SALK INSTITUTE FOR BIOLOGICAL STUDIES (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY JOSEPH HERDY, PHD ENTITLED: A2025010F BLOCKING JUMPING GENES TO STOP BRAIN INFLAMMATION IN ALZHEIMER'S DISEASE. INVESTIGATOR'S SUMMARY: ALZHEIMER'S DISEASE (AD) IS A FATAL NEURODEGENERATIVE DISEASE WITH NO AVAILABLE CURES. BY GENERATING PATIENT SPECIFIC INDUCED NEURONS (INS), WE FOUND THAT THERE IS A SMALL POPULATION OF INFLAMMATORY NEURONS THAT COULD BE TARGETED TO TREAT AD INSTEAD OF STRATEGIES THAT AFFECT THE ENTIRE BRAIN. HOWEVER, HOW THESE NEURONS BECOME INFLAMMATORY, AND THEREFORE WAYS TO INTERVENE ARE CURRENTLY UNKNOWN. IN THIS PROJECT, WE DEEPLY CHARACTERIZE A PROMISING GENETIC TARGET DRIVING INFLAMMATION, AND ASSESS IF BLOCKING ITS ACTIVITY IS A CANDIDATE FOR REVERSING HALLMARKS OF AD. NAME OF ORGANIZATION OR GOVERNMENT: VANDERBILT UNIVERSITY MEDICAL CENTER (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY MONICA SANTISTEBAN, PHD ENTITLED: A2025011S UNDERSTANDING THE CHOROID PLEXUS IN ALZHEIMER'S DISEASE. INVESTIGATOR'S SUMMARY: THE RENIN ANGIOTENSIN SYSTEM MAY PLAY AN IMPORTANT ROLE IN THE PROGRESSION OF PATHOLOGY IN ALZHEIMER'S DISEASE. IN THIS PROPOSAL, WE WILL LOOK AT THE CHOROID PLEXUS, A SMALL TISSUE WITHIN THE BRAIN THAT MAKES THE CEREBROSPINAL FLUID, AS A NOVEL SOURCE CONTRIBUTING TO THE LOCAL BRAIN RENIN ANGIOTENSIN SYSTEM AND COGNITIVE DECLINE IN AD. SINCE THERE ARE LIKELY A LOT MORE CHANGES HAPPENING IN THE CHOROID PLEXUS OTHER THAN THE RENIN ANGIOTENSIN SYSTEM, WE WILL ALSO ESTABLISH A COMPREHENSIVE DATABASE OF THE TRANSCRIPTIONAL CHANGES IN THE CHOROID PLEXUS IN AD TO SERVE AS A TOOL FOR FUTURE DISCOVERY. NAME OF ORGANIZATION OR GOVERNMENT: THE J. DAVID GLADSTONE INSTITUTES (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY KATERINA AKASSOGLOU, PHD ENTITLED: A2025013S UNRAVELING THE TRIGGERS TO MYELIN DAMAGE IN IN ALZHEIMER'S DISEASE. INVESTIGATOR'S SUMMARY: MYELIN DAMAGE HAS EMERGED AS A KEY PLAYER TO ALZHEIMER'S DISEASE (AD). HOWEVER, THE TRIGGERS OF MYELIN PATHOLOGY IN AD REMAIN LARGELY UNKNOWN. FIBRINOGEN, A BLOOD CLOTTING PROTEIN DEPOSITED IN AD BRAIN IS A POTENT INDUCER OF NEUROTOXIC INFLAMMATION AND INHIBITOR OF MYELIN REPAIR. WE WILL DETERMINE THE ROLE OF FIBRINOGEN ON MYELIN-FORMING CELLS IN AD MICE WITH STATE-OF-THE-ART IMAGING, MULTIOMIC TECHNOLOGIES, AND BEHAVIORAL ANALYSIS OF LEARNING AND MEMORY IN AD MICE, AS WELL AS TESTING PHARMACOLOGIC TREATMENTS PROMOTING REMYELINATION. NAME OF ORGANIZATION OR GOVERNMENT: MASSACHUSETTS GENERAL HOSPITAL (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY KSENIA KASTANENKA, PHD ENTITLED: A2025014S A SLEEPING PILL FOR ALZHEIMER'S DISEASE. INVESTIGATOR'S SUMMARY: ALZHEIMER'S DISEASE IS A MEMORY DISORDER WITHOUT AN EFFECTIVE CURE. DISRUPTIONS IN BRAIN ACTIVITY ASSOCIATED WITH SLEEP AND MEMORY IMPAIRMENTS ALZHEIMER'S PATIENTS EXPERIENCE COULD HOLD THE KEY TO DEVELOPMENT OF EFFECTIVE THERAPEUTIC STRATEGIES. SINCE ALZHEIMER'S PATIENTS SUFFER FROM SLEEP DISTURBANCES, ADMINISTRATION OF FDA-APPROVED SLEEPING PILLS COULD RESTORE THEIR SLEEP AND SLOW DISEASE PROGRESSION. THUS, WE WILL ADMINISTER PROVEN AND SAFE SLEEPING PILLS IN A MOUSE MODEL. THE RESULTS WILL INDICATE WHETHER SLEEPING PILLS COULD BE EFFECTIVE AT SLOWING ALZHEIMER'S DISEASE. NAME OF ORGANIZATION OR GOVERNMENT: INDIANA UNIVERSITY (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY MIGUEL MOUTINHO, PHARMD, PHD ENTITLED: A2025015S HOW DOES NIACIN PRODUCTION IN THE GUT ASSOCIATED TO ALZHEIMER'S DISEASE? INVESTIGATOR'S SUMMARY: ALZHEIMER'S DISEASE HAS BEEN CORRELATED WITH IMBALANCES IN GUT BACTERIA, HOWEVER, THE MECHANISTIC LINK BETWEEN DISEASE PROGRESSION AND GUT DYSBIOSIS HAVE NOT BEEN FULLY ELUCIDATED. IN THIS PROJECT, WE WILL TEST THE HYPOTHESIS THAT THE SYNTHESIS OF NIACIN IN THE GUT IS DYSREGULATED IN ALZHEIMER'S DISEASE, WHICH LEADS TO A REDUCED SUPPLY OF NIACIN TO BRAIN AND EXACERBATES THE DISEASE. CONVERSELY, WE WILL ASSESS IF INCREASING NIACIN SYNTHESIS IN THE GUT AND SUPPLY TO THE BRAIN CAN MITIGATE DISEASE PROGRESSION, WHICH COULD PAVE THE WAY FOR NOVEL THERAPEUTIC STRATEGIES AIMING AT GUT MICROBIOME. NAME OF ORGANIZATION OR GOVERNMENT: COLUMBIA UNIVERSITY (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY JAE-EUN MILLER, PHD ENTITLED: A2025016S REPAIRING THE BODY CLOCK TO DELAY ALZHEIMER'S DISEASE. INVESTIGATOR'S SUMMARY: BREAKDOWN IN CIRCADIAN RHYTHM IS BOTH A RISK FACTOR AND A SYMPTOM OF ALZHEIMER'S. THIS SUGGESTS A VICIOUS CYCLE OF CIRCADIAN DISRUPTION DRIVING DISEASE, AND DISEASE DRIVING CIRCADIAN DISRUPTION. IF WE COULD PREVENT CIRCADIAN DISRUPTION, WE MAY BE ABLE TO PREVENT DISEASE. THE ROOT CAUSE OF CIRCADIAN DYSFUNCTION IN ALZHEIMER'S IS UNCLEAR. TO ADDRESS THIS, WE WILL DETERMINE HOW TAUOPATHY, A KEY COMPONENT OF ALZHEIMER'S DISEASE, DISRUPTS THE FUNCTION OF THE MASTER CIRCADIAN CLOCK. WE WILL ALSO DEVELOP AN APPROACH RESTORE CIRCADIAN RHYTHM IN A DISEASE MODEL AND DETERMINE IF THIS PREVENTS DISEASE. PART II, LINE 1(H) CONTINUED NAME OF ORGANIZATION OR GOVERNMENT: BETH ISRAEL DEACONESS MEDICAL CENTER (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY FENG TIAN, PHD ENTITLED: A2025017S MONITORING NEURAL ACTIVITY AND NEUROINFLAMMATION IN ALZHEIMER'S DISEASE. INVESTIGATOR'S SUMMARY: NEUROINFLAMMATION IS ONE KEY HALLMARK OF ALZHEIMER'S DISEASE (AD) AND ONE OF THE MOST ATTRACTIVE DIRECTIONS FOR NOVEL AD DRUG DEVELOPMENT. HOWEVER, IT IS STILL UNCLEAR HOW NEUROINFLAMMATION CONTRIBUTES TO MEMORY LOSS AND COGNITIVE DEFICITS. WE WILL INNOVATIVELY LEVERAGE ADVANCED BRAIN MACHINE INTERFACE AND GENETIC TOOLS TO STUDY THE ROLE BETWEEN NEUROINFLAMMATION AND NEURAL ACTIVITY CHANGES DURING AD PROGRESSION. NAME OF ORGANIZATION OR GOVERNMENT: NORTHWESTERN UNIVERSITY - CHICAGO CAMPUS (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY JUSTYNA DOBROWOLSKA ZAKARIA, PHD ENTITLED: A2025019S AMYLOID PRECURSOR PROTEIN PROCESSING THROUGH A NOVEL PATHWAY IN ALZHEIMER'S DISEASE. INVESTIGATOR'S SUMMARY: ALTHOUGH APP, THE PARENT PROTEIN OF ABETA, WAS DISCOVERED 40 YEARS AGO, IT WASN'T UNTIL RECENTLY THAT A NEW CLEAVAGE PRODUCT OF APP WAS DETECTED IN HUMAN BIOFLUIDS. ETA-SECRETASE WAS FOUND TO CUT APP TO GENERATE AETA. AETA HAS BEEN SHOWN TO BE VERY IMPORTANT IN PROCESSES THAT PLAY A ROLE IN MEMORY FORMATION AND ITS LEVELS CHANGE IN MOUSE MODELS WHEN PROSPECTIVE AD THERAPIES ARE ADMINISTERED. NOT MUCH IS KNOWN ABOUT AETA IN HUMANS, AND THUS WE WANT TO DEVELOP A METHOD TO MEASURE HOW QUICKLY AETA IS PRODUCED AND CLEARED IN A HEALTHY OLDER HUMAN AND THEN COMPARE THIS TO AETA METABOLISM IN AD. NAME OF ORGANIZATION OR GOVERNMENT: WASHINGTON UNIVERSITY IN ST. LOUIS (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY CYRIL POTTIER, PHD ENTITLED: A2025020S EXPLORING THE ORIGIN AND COMPOSITION OF A UNIQUE PATHOLOGY IN ALZHEIMER'S DISEASE. INVESTIGATOR'S SUMMARY: SOME PEOPLE WITH EARLY-ONSET ALZHEIMER'S HAVE A RARE TYPE OF PATHOLOGY IN THE BRAIN CALLED "COTTON WOOL PLAQUES" (CWPS), BUT THEIR CAUSE IS STILL A MYSTERY. OUR RESEARCH WILL EXPLORE WHAT MAKES THESE PLAQUES UNIQUE, WHAT PROTEINS THEY CONTAIN COMPARED TO TYPICAL ALZHEIMER'S PLAQUES, AND WHETHER SPECIFIC GENES ARE INVOLVED. BY STUDYING CWPS, WE HOPE TO UNCOVER NEW INSIGHTS INTO HOW ALZHEIMER'S DEVELOPS AND WHY THE DISEASE VARIES BETWEEN PATIENTS. NAME OF ORGANIZATION OR GOVERNMENT: RESEARCH FOUNDATION OF SUNY - UNIVERSITY AT ALBANY (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY DAMIAN ZULOAGA, PHD ENTITLED: A2025021S INTERACTIONS OF PREGNANCY AND MENOPAUSE ON ALZHEIMER'S DISEASE OUTCOMES. INVESTIGATOR'S SUMMARY: WOMEN ARE DISPROPORTIONATELY AFFECTED BY ALZHEIMER'S DISEASE (AD) RELATIVE TO MEN. LIFE COURSE FACTORS UNIQUE TO WOMEN, INCLUDING PREGNANCY AND MENOPAUSE, LIKELY CONTRIBUTE TO FEMALE VULNERABILITY ALTHOUGH HOW THESE TWO FACTORS INTERACT TO AFFECT AD RELATED OUTCOMES IS UNKNOWN. WE PROPOSE TO USE A MOUSE MODEL OF AD TO DETERMINE HOW THE COMBINATION OF PREGNANCY AND MENOPAUSE IMPACT COGNITIVE/BEHAVIORAL FUNCTIONS AND AD ASSOCIATED NEUROPATHOLOGY. NAME OF ORGANIZATION OR GOVERNMENT: INDIANA UNIVERSITY (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY REBECCA WALLINGS, DPHIL ENTITLED: A2025023S UNDERSTANDING THE ROLE OF A SUPPRESSED IMMUNE SYSTEM IN FRONTOTEMPORAL DEMENTIA. INVESTIGATOR'S SUMMARY: I PREVIOUSLY PUBLISHED FINDINGS THAT SHOWED IMMUNE CELLS OUTSIDE OF THE BRAIN WHICH CARRY FTD-ASSOCIATED MUTATIONS HAVE A DAMPENED IMMUNE RESPONSE. A DAMPENED IMMUNE RESPONSE IS OFTEN ASSOCIATED WITH IMMUNE CELL EXHAUSTION (ICE); WHEN IMMUNE CELLS LOSE THE ABILITY TO RESPOND TO INFECTIONS AND INFLAMMATION. HERE WE WILL INVESTIGATE 1. THE DOWNSTREAM EFFECTS OF ICE ON OTHER IMMUNE CELLS, AND 2. HOW ICE IN THE PERIPHERY CONTRIBUTES TO DEGENERATION AND INFLAMMATION IN THE BRAIN. THE COMPLETION OF THIS PROPOSAL WILL INFORM US OF THE ROLE OF ICE IN FTD AND IF THIS IS A POTENTIAL THERAPEUTIC TARGET. NAME OF ORGANIZATION OR GOVERNMENT: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY JACK HUMPHREY, PHD ENTITLED: A2025024S TDP-43 IN THE AGING BRAIN: WHEN AND WHERE? INVESTIGATOR'S SUMMARY: DISEASES OF THE AGING BRAIN SUCH AS ALZHEIMER'S ARE CAUSED BY MULTIPLE FACTORS, INCLUDING THE PROTEINS AMYLOID AND TAU, BUT RECENTLY, AN ADDITIONAL PROTEIN TDP-43 HAS BEEN LINKED TO A FASTER DECLINE IN SOME PATIENTS. WE WILL INVESTIGATE TDP-43 IN A SET OF AUTOPSIED BRAINS FROM MULTIPLE DISEASES AND ASSOCIATE ITS PRESENCE TO THE PRESENCE OF AMYLOID AND TAU. WE WILL THEN STUDY WHICH SPECIFIC BRAIN CELLS CONTAIN CHANGES IN TDP-43 LEVELS AND WHAT THAT DOES TO THEM, WHICH COULD HELP TO UNDERSTAND HOW TDP-43 RELATES TO AGING AND DEMENTIA. NAME OF ORGANIZATION OR GOVERNMENT: THE OHIO STATE UNIVERSITY (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY HONGJUN FU, PHD ENTITLED: A2025025S PLCG2 VARIANTS AND THEIR IMPLICATIONS IN ALZHEIMER'S DISEASE. INVESTIGATOR'S SUMMARY: PLCG2, AN ENZYME THAT IS IMPORTANT IN CELL-TO-CELL COMMUNICATION, ALSO PLAYS A ROLE IN THE RISK OF DEVELOPING LATE ONSET ALZHEIMER'S DISEASE (AD). THE GENE THAT ENCODES FOR THIS ENZYME HAS AD-ASSOCIATED VARIANTS: ONE OF WHICH PROTECTS AGAINST AD, AND ONE OF WHICH PROMOTES AD. WE AIM TO IDENTIFY THE ROLE THAT THESE TWO AD-ASSOCIATED PLCG2 VARIANTS PLAY IN THE DEVELOPMENT AND PROGRESSION OF MICROTUBULE-ASSOCIATED PROTEIN TAU AGGREGATES, CELL DEATH, AND MEMORY LOSS. NAME OF ORGANIZATION OR GOVERNMENT: THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH BY TODD J. COHEN, PHD ENTITLED: A2025026S HARNESSING THE PROTEIN CHIP/STUB1 TO REDUCE ALZHEIMER'S BRAIN PATHOLOGY. INVESTIGATOR'S SUMMARY: THE RESEARCH FOCUSES ON THE ROLE OF THE PROTEIN CHIP/STUB1 IN ALZHEIMER'S DISEASE, PARTICULARLY ITS ABILITY TO PREVENT THE AGGREGATION OF TAU PROTEINS LINKED TO THE DISEASE'S PROGRESSION. BY ENGINEERING CHIP VARIANTS THAT ENHANCE ITS CHAPERONE FUNCTION, THE STUDY AIMS TO REDUCE TAU PATHOLOGY AND IMPROVE COGNITIVE FUNCTION IN ALZHEIMER'S PATIENTS. THIS INNOVATIVE APPROACH COULD LEAD TO NEW GENE THERAPIES FOR ALZHEIMER'S AND OTHER TAU-RELATED DISEASES. NAME OF ORGANIZATION OR GOVERNMENT: MAYO CLINIC, ROCHESTER (H) PURPOSE OF GRANT: NATIONAL GLAUCOMA RESEARCH BY GAVIN RODDY, MD, PHD ENTITLED: G2025001S DEVELOPING A NEW TREATMENT FOR GLAUCOMA THAT AVOIDS THE USE OF DAILY DROPS. INVESTIGATOR'S SUMMARY: GLAUCOMA IS THE LEADING CASE OF IRREVERSIBLE BLINDNESS WORLDWIDE. CURRENT TREATMENTS THAT REQUIRE DAILY INSTILLATION OF EYEDROPS TO LOWER PRESSURE CAUSE SIDE EFFECTS AND FAIL TO ADEQUATELY TREAT MANY PATIENTS. MY LAB DEVELOPED A PRESSURE-LOWERING DRUG THAT ACTS FOR 6 MONTHS WITH A SINGLE INJECTION. WE NOW SEEK TO TEST THIS DRUG IN A LARGE ANIMAL IN HOPES OF BRINGING A NEW THERAPY TO PATIENTS. PART II, LINE 1(H) CONTINUED NAME OF ORGANIZATION OR GOVERNMENT: UNIVERSITY OF CALIFORNIA, SAN DIEGO (H) PURPOSE OF GRANT: NATIONAL GLAUCOMA RESEARCH BY KARL JONAS WAHLIN, PHD ENTITLED: G2025002S REPAIRING THE HUMAN RETINA BY CELL REPROGRAMMING. INVESTIGATOR'S SUMMARY: RETINAL GANGLION CELL NEURONS CONNECT THE EYE TO THE BRAIN AND WHEN THEY DIE, WHETHER THROUGH GLAUCOMA OR THROUGH ACUTE TRAUMA, THIS LEADS TO PERMANENT VISION LOSS AND BLINDNESS. SIMILAR TO HOW THIS OCCURS THROUGHOUT THE ANIMAL KINGDOM, WE PROPOSE TO DEVELOP THE CAPABILITY TO DO THIS IN HUMAN RETINAL TISSUES THROUGH THE CONVERSION OF EXISTING MLLER CELLS IN THE EYE. NAME OF ORGANIZATION OR GOVERNMENT: UNIVERSITY OF WISCONSIN-MADISON (H) PURPOSE OF GRANT: NATIONAL GLAUCOMA RESEARCH BY ROB NICKELLS, PHD ENTITLED: G2025003S MITOCHONDRIA IN RETINAL GANGLION CELLS. INVESTIGATOR'S SUMMARY: RETINAL GANGLION CELLS RECEIVE INPUT FROM A TREE-LIKE DENDRITIC ARBOR THAT EXHIBITS PATHOLOGY AFTER OPTIC NERVE DAMAGE. THIS STUDY EXAMINES THE BIOLOGY OF ENERGY PRODUCING ORGANELLES CALLED MITOCHONDRIA IN ARBOR PATHOLOGY INCLUDING HOW SPECIALIZED CELLS CALLED MICROGLIA PARTICIPATE IN THIS PROCESS. NAME OF ORGANIZATION OR GOVERNMENT: DUKE UNIVERSITY SCHOOL OF MEDICINE (H) PURPOSE OF GRANT: NATIONAL GLAUCOMA RESEARCH BY DAN STAMER, PHD ENTITLED: G2025004S ROLE OF A KEY GENE, ANGPTL7 IN STEROID-INDUCED GLAUCOMA. INVESTIGATOR'S SUMMARY: GLUCOCORTICOIDS ARE WIDELY USED ANTI-INFLAMMATORY DRUGS THAT TREAT A VARIETY OF DISEASES, BUT LONG-TERM USE OFTEN RESULTS IN ELEVATED EYE PRESSURE THAT CAN LEAD TO GLAUCOMA. USING THE MOST ADVANCED RESEARCH TECHNOLOGIES, THE PRESENT PROJECT IS DESIGNED TO UNDERSTAND HOW ANGPTL7, A GLAUCOMA RISK GENE, IS INVOLVED IN ELEVATING EYE PRESSURE AFTER GLUCOCORTICOID TREATMENT. NAME OF ORGANIZATION OR GOVERNMENT: UNIVERSITY OF SOUTHERN CALIFORNIA (H) PURPOSE OF GRANT: NATIONAL GLAUCOMA RESEARCH BY BENJAMIN XU, MD, PHD ENTITLED: G2025005S ENHANCING ACCESS TO GLAUCOMA CARE USING ARTIFICIAL INTELLIGENCE. INVESTIGATOR'S SUMMARY: GLAUCOMA IS THE MOST COMMON CAUSE OF IRREVERSIBLE VISION LOSS WORLDWIDE. A PUBLIC HEALTH CRISIS IS EMERGING DUE TO THE RAPID RISE IN GLAUCOMA PREVALENCE, SHORTAGE OF EYECARE PROVIDERS, AND GLARING ACCESS AND EQUITY ISSUES. WE PROPOSE TO INTEGRATE TELEOPHTHALMOLOGY AND ARTIFICIAL INTELLIGENCE (AI) TO ENHANCE THE DELIVERY OF HIGH-QUALITY, REPRODUCIBLE, EQUITABLE, RESOURCE-EFFICIENT GLAUCOMA CARE. NAME OF ORGANIZATION OR GOVERNMENT: GOOD SAMARITAN FOUNDATION (H) PURPOSE OF GRANT: NATIONAL GLAUCOMA RESEARCH BY BRAD FORTUNE, OD, PHD ENTITLED: G2025007S ASSESSMENT OF VASCULAR RESISTANCE IN GLAUCOMA. INVESTIGATOR'S SUMMARY: ABNORMAL BLOOD FLOW WITHIN THE EYE IS THOUGHT TO BE ONE FACTOR CONTRIBUTING TO THE DEVELOPMENT AND PROGRESSION OF GLAUCOMA. HOWEVER, QUESTIONS REMAIN ABOUT HOW AND WHEN THIS OCCURS. OUR PROPOSAL AIMS TO DETERMINE WHETHER VASCULAR RESISTANCE IS ELEVATED DURING EARLY STAGES OF GLAUCOMA. OUR RESULTS WILL CONTRIBUTE IMPORTANT KNOWLEDGE AND USEFUL DIAGNOSTIC TOOLS TO THE GLAUCOMA RESEARCH COMMUNITY. NAME OF ORGANIZATION OR GOVERNMENT: THE SCHEPENS EYE RESEARCH INSTITUTE, INC. (H) PURPOSE OF GRANT: NATIONAL GLAUCOMA RESEARCH BY TATJANA JAKOBS, MD ENTITLED: G2025008S INTERLEUKIN-10 AS A NEUROPROTECTIVE FACTOR IN GLAUCOMA. INVESTIGATOR'S SUMMARY: VISUAL IMPAIRMENT IN GLAUCOMA IS CAUSED BY THE DEGENERATION AND EVENTUAL DEATH OF RETINAL GANGLION CELLS THROUGH MECHANISMS THAT ARE NOT FULLY UNDERSTOOD. RETINAL MICROGLIA CAN PLAY NEUROPROTECTIVE AND NEUROTOXIC ROLES IN GLAUCOMA. WE IDENTIFIED IL10 AS A CANDIDATE FOR A MICROGLIA-DERIVED FACTOR THAT MAY SELECTIVELY BOOST THE NEUROPROTECTIVE EFFECTS. NAME OF ORGANIZATION OR GOVERNMENT: UNIVERSITY OF CALIFORNIA, IRVINE (H) PURPOSE OF GRANT: NATIONAL GLAUCOMA RESEARCH BY DOROTA SKOWRONSKA-KRAWCZYK, PHD ENTITLED: G2025009S ROLE OF IOP ELEVATION IN INCREASING VULNERABILITY OF RETINA TO STRESS. INVESTIGATOR'S SUMMARY: AGING, A PROCESS WHERE DAMAGE ACCUMULATES IN OUR CELLS OVER TIME, MAKES TISSUES MORE SENSITIVE TO ELEVATED INTRAOCULAR PRESSURE (IOP). HOWEVER, IT IS UNKNOWN HOW CELLS BECOME MORE VULNERABLE AS THEY AGE. OUR EXPERIMENTS WILL EXPLORE HOW RETINAS RESPOND TO IOP-RELATED STRESS AND THE MECHANISMS BEHIND THIS VULNERABILITY, AIMING TO FIND NEW WAYS TO PROTECT RETINAL NEURONS FROM GLAUCOMATOUS CHANGES. NAME OF ORGANIZATION OR GOVERNMENT: UNIVERSITY OF WISCONSIN-MADISON (H) PURPOSE OF GRANT: NATIONAL GLAUCOMA RESEARCH BY COLLEEN MCDOWELL, PHD ENTITLED: G2025010S NOVEL MECHANISMS REGULATING PRESSURE IN THE EYE. INVESTIGATOR'S SUMMARY: ELEVATED PRESSURE IN THE EYE IS A MAJOR RISK FACTOR FOR GLAUCOMA AND IS DUE TO FLUID BUILDUP AND IMPROPER DRAINAGE IN THE EYE. IT IS KNOWN THAT FLUID DRAINAGE FROM THE EYE IS NOT UNIFORM CIRCUMFERENTIALLY, AND THIS STUDY AIMS TO STUDY HOW THESE SEGMENTAL DIFFERENCES IN FLUID FLOW ARE DEVELOPED AND REGULATED. THESE DATA WILL HELP IDENTIFY NOVEL MECHANISMS TO LOWER PRESSURE IN THE EYE. NAME OF ORGANIZATION OR GOVERNMENT: WILLIAM MARSH RICE UNIVERSITY (H) PURPOSE OF GRANT: MACULAR DEGENERATION RESEARCH BY JERZY SZABLOWSKI, PHD ENTITLED: M2025001N A BLOOD TEST TO MEASURE GENES ASSOCIATED WITH MACULAR DEGENERATION. INVESTIGATOR'S SUMMARY: ONE CAN GAIN A LOT OF INFORMATION FROM EXCISING A TISSUE AND ANALYZING ITS BIOCHEMICAL BEHAVIOR, SUCH AS EXPRESSION OF GENES UNDERLYING DISEASE. HOWEVER, FOR THE RETINA SUCH EXCISION IS IMPOSSIBLE AS IT WOULD RESULT IN VISION LOSS. WE ARE USING A CUTTING-EDGE TECHNOLOGY TO MEASURE ACTIVITY OF GENES WITHIN THE RETINA WITH A BLOOD TEST. SPECIFICALLY, WE ARE FOCUSING ON TWO GENES THAT ARE SUSPECTED OF INCREASING THE RISK OF DEVELOPING A VISION DISORDER CALLED AGE-RELATED MACULAR DEGENERATION. IF WE ARE SUCCESSFUL, DOCTORS COULD MEASURE EXPRESSION OF PATIENTS GENES IN RETINA WITHOUT DAMAGING IT. PART II, LINE 1(H) CONTINUED NAME OF ORGANIZATION OR GOVERNMENT: UNIVERSITY OF OKLAHOMA HEALTH SCIENCES CENTER (H) PURPOSE OF GRANT: MACULAR DEGENERATION RESEARCH BY ANA J CHUCAIR-ELLIOTT, PHD ENTITLED: M2025002N THE ROLE OF AGING, DIET, AND INFLAMMATION IN RPE DEGENERATIVE PROCESSES. INVESTIGATOR'S SUMMARY: AMD IS A BLINDING DISEASE IN WHICH THE CELLS THAT PROCESS VISUAL INFORMATION, PHOTORECEPTORS, DEGENERATE AND DIE. THIS NEURODEGENERATION IS PARTLY DUE TO FAILURE OF THE RETINAL PIGMENTED EPITHELIUM (RPE), THE TISSUE THAT LIES BENEATH THE RETINA, TO SUPPORT NORMAL TISSUE STRUCTURE AND VISUAL FUNCTION. AGING IS THE MAIN RISK FACTOR FOR AMD, BUT DIET AND INFLAMMATION ALSO INCREASE AMD RISK. OUR PROPOSED RESEARCH AIMS TO STUDY HOW AGING AND DIET INTERACT WITH IMMUNE CELLS, MICROGLIA AND MACROPHAGES, TO AFFECT THE RPE GENETIC PROGRAMS AND FUNCTION FOR DISCOVERY OF CANDIDATE TARGETS TO TREAT AMD. NAME OF ORGANIZATION OR GOVERNMENT: NATIONAL EYE INSTITUTE, NIH (H) PURPOSE OF GRANT: MACULAR DEGENERATION RESEARCH BY RUCHI SHARMA, PHD ENTITLED: M2025003N STUDYING THE ROLE OF GENES & THE TONE OF OUR EYE PIGMENT IN AMD. INVESTIGATOR'S SUMMARY: AMD IS A COMMON EYE DISEASE AFFECTING MANY PEOPLE WORLDWIDE. CAUCASIANS ARE MORE LIKELY TO DEVELOP AMD THAN BLACK INDIVIDUALS. WE WILL USE MODELS CREATED FROM PATIENT STEM CELL-DERIVED RETINAL PIGMENT EPITHELIUM AND CHOROID TO EXPLORE THE CELLULAR PROCESSES THAT MAKE SOME PEOPLE MORE VULNERABLE TO AMD WHILE OTHERS RESIST IT. OUR GOAL IS TO UNDERSTAND HOW PIGMENTATION, CERTAIN GENETIC FACTORS, AND CELLULAR PROCESSES CONTRIBUTE TO THE RISK OF AMD. THIS RESEARCH WILL HELP US UNCOVER HOW SOME PEOPLE RESIST AMD, WHICH MAY LEAD TO NEW DRUGS TO TREAT OR PREVENT THE DISEASE. NAME OF ORGANIZATION OR GOVERNMENT: LELAND STANFORD JUNIOR UNIVERSITY (H) PURPOSE OF GRANT: MACULAR DEGENERATION RESEARCH BY CHARLES DEBOER, MD, PHD ENTITLED: M2025004N MICROFABRICATED IMPLANT TO TREAT AGE-RELATED MACULAR DEGENERATION. INVESTIGATOR'S SUMMARY: THERAPEUTICS TO TREAT AGE-RELATED MACULAR DEGENERATION (AMD) ARE INJECTED INTO THE VITREOUS, WHILE THE ACTUAL SITE OF PATHOLOGY OCCURS DEEPER IN THE EYE, AT THE LEVEL OF THE CHOROID AND RETINA. THE SUPRACHOROIDAL SPACE IS IN DIRECT CONTACT WITH PATHOLOGIC VESSELS IN WET AMD AND DIRECT TARGETING COULD INCREASE LOCAL DRUG CONCENTRATIONS AND POSSIBLY IMPROVE EFFICACY. WE PROPOSE USING A NOVEL DEVICE CONSISTING OF A REFILLABLE DRUG RESERVOIR AND A TINY TUBE INSERTED INTO THE SUPRACHOROIDAL SPACE FOR EXTENDED LOCALIZED DRUG DELIVERY, PROVIDING A NEW WAY TO TREAT AMD. NAME OF ORGANIZATION OR GOVERNMENT: LELAND STANFORD JUNIOR UNIVERSITY (H) PURPOSE OF GRANT: MACULAR DEGENERATION RESEARCH BY MOHAJEET BALVEER BHUCKORY, PHD ENTITLED: M2025007N ELECTRONIC IMPLANTS FOR RESTORING SHARP VISION IN MACULAR DEGENERATION. INVESTIGATOR'S SUMMARY: IN ADVANCED AMD, THE LOSS OF THE LIGHT-SENSITIVE CELLS IN THE CENTRAL RETINA, PHOTORECEPTORS (PR), LEAD TO BLINDNESS. HOWEVER, THE REMAINING CONNECTING NEURONS THAT RELAY VISUAL SIGNALS TO THE BRAIN STAY MOSTLY INTACT. OUR CURRENT ELECTRONIC PHOTORECEPTORS (EPR) CAN STIMULATE THESE NEURONS, RESTORING THE FLOW OF VISUAL INFORMATION TO THE BRAIN. THIS PROJECT AIMS TO SIGNIFICANTLY ENHANCE THE RESOLUTION BY DEVELOPING CUTTING-EDGE, CELL-SIZED EPR IMPLANTS, OFFERING THE POTENTIAL TO IMPROVE PROSTHETIC VISION BEYOND LEGAL BLINDNESS AND APPROACH NATURAL VISION. NAME OF ORGANIZATION OR GOVERNMENT: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO (H) PURPOSE OF GRANT: MACULAR DEGENERATION RESEARCH BY VALENCIA FERNANDES, PHD ENTITLED: M2025008F HOW METABOLIC STRESS CAN DRIVE MACULAR DEGENERATION. INVESTIGATOR'S SUMMARY: AGE-RELATED MACULAR DEGENERATION (AMD) IS CAUSED BY DAMAGE TO THE RETINAL PIGMENT EPITHELIUM (RPE), WHICH NOURISHES AND SUPPORTS THE RETINA. CHRONIC INFLAMMATION, LIPID ACCUMULATION, AND MITOCHONDRIAL INJURY ACT TOGETHER TO COMPROMISE RPE HEALTH, BUT EXACTLY HOW THIS OCCURS IS NOT WELL UNDERSTOOD. THIS RESEARCH PROPOSES TO IDENTIFY THE KEY PLAYERS IN THIS PROCESS BY FOCUSING ON A PROTEIN CALLED STAT3, WHICH IS A MASTER REGULATOR OF CELL HEALTH, AND INVESTIGATE WHETHER IT CAN BE A DRUG TARGET IN AMD. NAME OF ORGANIZATION OR GOVERNMENT: DUKE UNIVERSITY SCHOOL OF MEDICINE (H) PURPOSE OF GRANT: MACULAR DEGENERATION RESEARCH BY DR. NOBUHIKO SHIRAKI, PHD ENTITLED: M2025011F MICROGLIA'S ROLES IN AMD TO INFORM THERAPIES FOR VISION LOSS PREVENTION. INVESTIGATOR'S SUMMARY: OUTER RETINAL DISEASES, LIKE AMD, CAUSE PERMANENT VISION LOSS DUE TO DAMAGE TO LIGHT-SENSITIVE CELLS. WHILE SOME IMMUNE CELLS HELP CLEAR HARMFUL DEBRIS, RECENT FINDINGS SUGGEST DISTINCT SUBTYPES WITH DIFFERENT FUNCTIONS. GENETIC ANALYSIS IDENTIFIED TWO SUBTYPES IN A CERTAIN IMMUNE CELL, ONE OF WHICH MAY WORSEN INFLAMMATION. STUDIES WITH GENETICALLY MODIFIED MICE SHOWED THAT REDUCING CERTAIN MOLECULES IN THESE CELLS REDUCED RETINAL DAMAGE AFTER LIGHT EXPOSURE. THIS RESEARCH AIMS TO CLARIFY THE IMMUNE CELL ROLES IN AMD, AIMING TO INFORM THERAPIES FOR PREVENTION OF VISION LOSS IN AMD PATIENTS. NAME OF ORGANIZATION OR GOVERNMENT: UNIVERSITY OF IDAHO (H) PURPOSE OF GRANT: MACULAR DEGENERATION RESEARCH BY ASHLEY FARRE, PHD ENTITLED: M2025012F SHAPING OF NEURONAL CONNECTIONS BY RESIDENT IMMUNE CELLS. INVESTIGATOR'S SUMMARY: IN LATE STAGES OF AGE-RELATED MACULAR DEGENERATION (AMD), LIGHT SENSING CELLS (PHOTORECEPTORS) IN THE EYE DIE, LEADING TO VISION LOSS. TO TREAT THIS WITH FUTURE APPROACHES, WE CAN POTENTIALLY REPLACE PHOTORECEPTORS, BUT IN ORDER TO WORK PROPERLY, THESE CELLS NEED TO BE ABLE TO COMMUNICATE WITH OTHER NEURONS IN THE EYE THAT PROCESS LIGHT INFORMATION AND PASS IT TO THE BRAIN. WITH THIS PROJECT, WE WILL DETERMINE HOW MICROGLIA (IMMUNE CELLS OF THE EYE) COULD HELP NEW PHOTORECEPTORS ESTABLISH CONNECTIONS WITH OTHER NEURONS, POTENTIALLY MAKING FUTURE AMD TREATMENTS MORE EFFECTIVE. NAME OF ORGANIZATION OR GOVERNMENT: UNIVERSITY OF CALIFORNIA, SAN DIEGO (H) PURPOSE OF GRANT: MACULAR DEGENERATION RESEARCH BY JAESOO JUNG, PHD ENTITLED: M20250013F HEPARAN SULFATE REGULATION OF HTRA1-MEDIATED PROTEOSTASIS IN BRUCH'S MEMBRANE IN AGE-RELATED MACULAR DEGENERATION. INVESTIGATOR'S SUMMARY: HTRA1 IS A STRONG GENETIC RISK FACTOR FOR AGE-RELATED MACULAR DEGENERATION (AMD), BUT ITS NATURAL SUBSTRATES IN BRUCH'S MEMBRANE (BRM) REMAIN UNKNOWN. TO UNCOVER HOW ALTERED HTRA1 PROTEOLYSIS CONTRIBUTES TO DRUSEN FORMATION, WE WILL USE ISOTOPE-LABELING DEGRADOMICS TO IDENTIFY ITS ENDOGENOUS SUBSTRATES. WE WILL THEN DEVELOP A HIGH-TIME-RESOLVING HOMOGENEOUS TIME-RESOLVED FLUORESCENCE (HTRF) ASSAY TO EVALUATE HOW HEPARAN SULFATES MODULATE HTRA1-MEDIATED HYDROLYSIS OF THESE CANDIDATE SUBSTRATES, PROVIDING INSIGHT INTO MECHANISMS DRIVING EARLY AMD PATHOLOGY. PART II, LINE 1(H) CONTINUED NAME OF ORGANIZATION OR GOVERNMENT: MAYO CLINIC, JACKSONVILLE (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH ENTITLED: CA2021010 MOLECULAR NEURODEGENERATION JOURNAL. INVESTIGATOR'S SUMMARY: THE AIM OF MOLECULAR NEURODEGENERATION (MN) JOURNAL (HTTPS://MOLECULARNEURODEGENERATION.BIOMEDCENTRAL.COM/) IS TO SERVE THE SCIENTIFIC COMMUNITY BY PUBLISHING HIGH-IMPACT, HIGH-QUALITY, AND FRONT-LINE RESEARCH DISCOVERIES IN DIVERSE AREAS OF NEURODEGENERATIVE DISEASES INCLUDING ALZHEIMER'S DISEASE AND EYE-RELATED DEGENERATIVE CONDITIONS. MN IS THE OFFICIAL JOURNAL OF THE BRIGHTFOCUS FOUNDATION. THE OPEN ACCESS PUBLISHING MODEL PROVIDES FREE ARTICLES TO THE GENERAL PUBLIC, AS WELL AS SCIENTISTS, CLINICIANS, AND OTHER HEALTHCARE. THE JOURNAL HAS SEEN FURTHER GROWTH IN RECENT YEARS IN PARTICULAR IN THE AREA OF SCIENTIFIC IMPACT AND REPUTATION. SOME OF THESE ARE REFLECTED IN THE FOLLOWING METRICS: 1) 1,877,858 DOWNLOADS IN 2024; 2) JOURNAL CITATION REPORTS (JCR) TRACKED CITATIONS: 9,015 IN 2022; 9,806 IN 2023; AND 11,362 IN 2024; 3) JOURNAL IMPACT FACTOR: 15.1 IN 2022; 15.1 IN 2023; 17.5 IN 2024; 4) 2024 JCR RANKING: MOLECULAR NEURODEGENERATION RANKED NO. 4 AMONG 314 NEUROSCIENCE JOURNALS (WITHIN THE TOP 1.1%). NAME OF ORGANIZATION OR GOVERNMENT: INTERNATIONAL SOCIETY FOR MOLECULAR NEURODEGENERATION (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH ENTITLED: CA2021011 INTERNATIONAL SOCIETY FOR MOLECULAR NEURODEGENERATION. INVESTIGATOR'S SUMMARY: THIS AWARD IS FOR THE CREATION, AND GROWTH OF, THE "INTERNATIONAL SOCIETY FOR MOLECULAR NEURODEGENERATION" (ISMND) AND SUPPORT OF ITS BI-ANNUAL MEETINGS AND EDUCATIONAL AND SCIENTIFIC PURPOSES. ISMND'S MISSION IS TO SERVE AS AN ACCELERATOR FOR THE CONTINUOUS IMPROVEMENT OF BRAIN AND EYE HEALTH AND WELL-BEING BY CREATING A MULTIDISCIPLINARY GLOBAL PLATFORM FOR SCIENTISTS, PHYSICIANS, AND THE PUBLIC FROM DIFFERENT FACETS AND SCIENTIFIC DISCIPLINES TO MORE READILY CONNECT, SHARE AND COMMUNICATE SCIENTIFIC DISCOVERIES, AND DEVELOP CURES FOR NEURODEGENERATIVE DISEASES, IN THE HOPES OF A WORLD FREE OF BRAIN AND EYE DISEASES. NAME OF ORGANIZATION OR GOVERNMENT: MEDICAL TECHNOLOGY ENTERPRISE CONSORTIUM (H) PURPOSE OF GRANT: ALZHEIMER'S DISEASE RESEARCH ENTITLED: CA2025003 THE CONCUSSION ASSESSMENT, RESEARCH, & EDUCATION (CARE) CONSORTIUM BIOBANK. INVESTIGATOR'S SUMMARY: THE OVERARCHING GOAL IS TO LEVERAGE THE DEEPLY ENRICHED CARE COHORT OF MALE AND FEMALE COLLEGIATE ATHLETES AND MILITARY PERSONNEL WITH AND WITHOUT MILD TBI (MTBI)/CONCUSSION AND/OR REPETITIVE HEAD IMPACT EXPOSURE, TO DETERMINE IF A PANEL OF ADRD GENOMIC FACTORS CAN IDENTIFY YOUNG ADULTS (3RD AND 4TH DECADE OF LIFE) WITH VERY EARLY INDICATORS CONSISTENT WITH PRECLINICAL ADRD, WHO MIGHT BENEFIT FROM PRIMARY PREVENTIVE STRATEGIES (ELIMINATION OF HEAD IMPACT EXPOSURE), OR EARLY CONSIDERATION OF RECENTLY APPROVED DISEASE MODIFYING THERAPIES (DMTS). X X X X X 0 0 0 0 0 0 0 0 0 STACY PAGOS HALLER PRESIDENT/CEO 423113 0 0 0 1715 0 0 0 46677 0 471505 0 0 0 NANCY KEACH SR. VP, STRATEGIC PARTNERSHIPS 268573 0 0 0 1584 0 0 0 51713 0 321870 0 0 0 R BRIAN ELDERTON SR. VP, DEVELOPMENT 259608 0 0 0 1715 0 0 0 40046 0 301369 0 0 0 JONATHAN WALSH SVP, FINANCE & ADMINISTRATION 226326 0 0 0 460 0 0 0 4251 0 231037 0 0 0 DIANE BOVENKAMP PHD VP, SCIENTIFIC AFFAIRS 195690 0 0 0 552 0 0 0 24358 0 220600 0 0 0 SHARYN ROSSI - PHD DIR OF SCIENT. PROGRAMS, NEUROSCIENCE 125492 0 0 0 240 0 0 0 42143 0 167875 0 0 0 LISA MORGAN SENIOR DIRECTOR, ANNUAL GIVING 134563 0 0 0 552 0 0 0 22867 0 157982 0 0 0 PREETI SUBRAMANIAN - PHD DIR OF SCIENT. PROGRAMS, VISION SCIENCE 139571 0 0 0 360 0 0 0 16400 0 156331 0 0 0 PART I, LINE 3 THE LAST COMPENSATION SURVEY WAS COMPLETED ON 3/9/2022. X 45 394954 FMV 0 1 1 PART I, COLUMN (B): BRIGHTFOCUS REPORTS THE NUMBER OF CONTRIBUTIONS IN PART I, COLUMN B. PART I, LINE 32B: BRIGHTFOCUS ENGAGED THE SERVICES OF A COMMERCIAL REAL ESTATE BROKER TO SOLICIT AND SELL THE COMMERCIAL REAL ESTATE DONATED TO THE ORGANIZATION 25 YEARS AGO. FORM 990, PART III, LINE 1, DESCRIPTION OF ORGANIZATION MISSION: BRIGHTFOCUS FOUNDATION FUNDS EXCEPTIONAL RESEARCH WORLDWIDE TO DEFEAT ALZHEIMER'S DISEASE, MACULAR DEGENERATION, AND GLAUCOMA AND PROVIDES EXPERT INFORMATION ON THESE HEARTBREAKING DISEASES. OUR VISION IS: A WORLD FREE FROM DISEASES OF MIND AND SIGHT. COLLECTIVELY, MORE THAN 300 MILLION PEOPLE WORLDWIDE SUFFER FROM THESE DISEASES. BRIGHTFOCUS HAS A PROVEN TRACK RECORD OF SUPPORTING THE MOST INNOVATIVE, EARLY-STAGE RESEARCH SEEKING TO FOSTER A BETTER UNDERSTANDING OF, TREATMENTS FOR, AND ULTIMATELY, A CURE FOR, THESE AGE-RELATED DISEASES WITH NO CURE. SINCE 1973, BRIGHTFOCUS HAS AWARDED MORE THAN $310 MILLION IN RESEARCH GRANTS TO THOUSANDS OF SCIENTISTS IN 28 COUNTRIES THROUGH ITS THREE PROGRAMS: ALZHEIMER'S DISEASE RESEARCH, MACULAR DEGENERATION RESEARCH, AND NATIONAL GLAUCOMA RESEARCH. THE RESEARCH WE SUPPORT IS CAREFULLY CHOSEN BY OUR SCIENTIFIC REVIEW COMMITTEES, COMPRISING WORLD-RENOWNED RESEARCHERS AND LEADERS IN THEIR FIELDS. OUR RESEARCH FUNDING HAS LED TO MAJOR CONTRIBUTIONS TO UNDERSTANDING, DIAGNOSING, PREVENTING, AND TREATING THESE DISEASES AND PROVIDES SUPPORT FOR SCIENTISTS WHO HAVE RECEIVED PRESTIGIOUS AWARDS, INCLUDING TWO NOBEL PRIZES. AN INDICATOR OF OUR ABILITY TO PUSH NEW BOUNDARIES OF KNOWLEDGE IS THAT BRIGHTFOCUS FUNDED GRANTEES WERE ABLE TO OBTAIN 8 TIMES THE ORIGINAL FUNDING AMOUNT PROVIDED BY BRIGHTFOCUS, TO CONTINUE TO DEVELOP THEIR INNOVATIONS. THE WORLD-CLASS RESEARCH IDENTIFIED AND SUPPORTED BY BRIGHTFOCUS IS ON THE CUTTING EDGE OF THE FIGHT TO SAVE MIND AND SIGHT. OUR FUNDING ACTS AS A CATALYST IN EARLY-STAGE RESEARCH, AND BRIGHTFOCUS RESEARCH PROGRAMS ARE DESIGNED TO PROVIDE INITIAL FUNDING FOR HIGHLY INNOVATIVE EXPERIMENTAL IDEAS. DUE TO THE STRUCTURED GRANT REVIEW AND APPROVAL PROCESS, THE RESEARCH IMPACT OF BRIGHTFOCUS IS VERY HIGH. MOST RECIPIENTS OF BRIGHTFOCUS FUNDING GO ON TO RECEIVE FUTURE GRANTS FROM OTHER SOURCES THAT ARE UP TO 8 TIMES LARGER THAN THE ORIGINAL BRIGHTFOCUS AWARD. THIS HIGH RETURN ON BRIGHTFOCUS INVESTMENT SPEAKS TO OUR ABILITY TO IDENTIFY PROMISING RESEARCH IN ITS EARLIEST STAGES AND SPAWN FUTURE SCIENTIFIC DISCOVERIES. IT IS OUR FIRM BELIEF THAT HAVING THE COURAGE TO INVEST IN INNOVATIVE IDEAS WILL LEAD TO REVOLUTIONARY APPROACHES AND LIFE-SAVING BREAKTHROUGHS. ALONG WITH FUNDING CUTTING-EDGE RESEARCH TO FIND CURES FOR SOME OF THE WORLD'S COSTLIEST DISEASES, BRIGHTFOCUS ALSO PROVIDES FREE, EXPERT-VETTED EDUCATIONAL MATERIALS TO HUNDREDS OF THOUSANDS OF PEOPLE IMPACTED BY THESE DISEASES NATIONWIDE. WE GROUND THESE EDUCATIONAL MATERIALS IN THE LATEST RESEARCH FINDINGS AND BREAKTHROUGHS. BRIGHTFOCUS ALSO INCREASES PUBLIC AWARENESS OF ALZHEIMER'S, MACULAR DEGENERATION, AND GLAUCOMA, AND COMMUNICATES WITH THOUGHT LEADERS AND ELECTED OFFICIALS ABOUT THE IMPORTANCE OF SCIENTIFIC RESEARCH IN THESE AREAS. BRIGHTFOCUS' AWARD-WINNING PUBLIC SERVICE ANNOUNCEMENTS (PSAS) HAVE APPEARED ON TELEVISION, RADIO, AND IN PRINT THROUGHOUT THE NATION. THE IMPACT OF ALZHEIMER'S, MAKE A PLAN TODAY: GET YOUR EYES CHECKED, AND FINDING ANSWERS IN THE FIGHT AGAINST ALZHEIMER'S SEEK TO RAISE AWARENESS ABOUT THESE DISEASES AND THE IMPORTANCE OF EARLY DETECTION. SIMILAR MESSAGES HAVE BEEN DELIVERED THROUGH DONATED PRINT PSA SPACE IN AIRPORTS AND TRAIN STATIONS, AS WELL AS AT PHARMACIES, SUPERMARKETS AND DIGITALLY. IN FISCAL YEAR 2025, THESE PSA MESSAGES GENERATED $9,240,763 IN DONATED MEDIA SERVICES AND GARNERED OVER 425 MILLION IMPRESSIONS. WE CONTINUE TO INCREASE OUR PRINT PUBLICATIONS, MANY IN SPANISH, THAT PROVIDE HELPFUL INFORMATION TO PATIENTS AND CAREGIVERS, AND REGULARLY PRODUCE NEW VIDEO AND AUDIO RESOURCES IN CONJUNCTION WITH ALLIES IN THE MEDICAL AND SCIENTIFIC COMMUNITIES. PARTNERING WITH SEVERAL HIGH-PROFILE PUBLIC AND PRIVATE ORGANIZATIONS, BRIGHTFOCUS IS HELPING TO BETTER EDUCATE THE PUBLIC ON THE LATEST RESEARCH DEVELOPMENTS PERTAINING TO ALZHEIMER'S, MACULAR DEGENERATION, AND GLAUCOMA, AS WELL AS THE IMPORTANCE OF EQUITABLE PARTICIPATION IN CLINICAL RESEARCH TO ACCELERATE THE PATH TO CURES FOR NEURODEGENERATIVE DISEASES. SPECIFICALLY, BRIGHTFOCUS PRODUCES AND DISSEMINATES FREE PROGRAMS INCLUDING: BRIGHTFOCUS VISION CHATS. SINCE 2014, THESE AUDIO DISCUSSIONS HAVE BROUGHT TOGETHER PATIENTS AND CAREGIVERS FOR INTERACTIVE MONTHLY TELEPHONE FORUMS TO LEARN FROM AND ASK QUESTIONS OF LEADING VISION DISEASE EXPERTS. THE CHATS ARE ARCHIVED ON OUR WEBSITE, WITH AUDIO AND PRINT TRANSCRIPTS AVAILABLE IN SEVERAL ACCESSIBLE FORMATS ONLINE, INCLUDING AS PODCASTS ON SPOTIFY AND APPLE ITUNES. ZOOM IN ON DEMENTIA AND ALZHEIMER'S, A MONTHLY VIRTUAL DISCUSSION OPEN TO THE PUBLIC FEATURING WORLD-RENOWNED RESEARCH SCIENTISTS WHO SHARE THE LATEST BREAKTHROUGHS AND FINDINGS IN THE FIELD. ALL EPISODES ARE RECORDED AND AVAILABLE TO WATCH ON DEMAND ON OUR WEBSITE AND YOUTUBE. WE REGULARLY PUBLISH ARTICLES AND RESOURCES PROVIDING LAY-PERSON INFORMATION ABOUT COMMONLY ASKED DISEASE QUESTIONS. TWO MILLION VISITORS EACH YEAR TO OUR WEBSITE, WWW.BRIGHTFOCUS.ORG, FIND A WEALTH OF INFORMATION ON RESEARCH, SYMPTOMS, TREATMENTS, AND CAREGIVER SUPPORT. BRIGHTFOCUS IS A PRESENTING PARTNER OF SEVERAL DOCUMENTARY FILMS, INCLUDING TAKING CARE, REMEMBERING GENE WILDER, AND GLEN CAMPBELL: I'LL BE ME, AND EXECUTES ASSOCIATED EDUCATIONAL IMPACT CAMPAIGNS. THESE FILMS ARE SHOWN IN COMMUNITY SETTINGS ACROSS THE COUNTRY TO INCREASE AWARENESS OF, AND PARTICIPATION IN, ALZHEIMER'S CLINICAL RESEARCH. BRIGHTFOCUS HAS A LONG-RUNNING AND ROBUST DIRECT MAIL PROGRAM ACROSS THE THREE RESEARCH AREAS IT SUPPORTS. BRIGHTFOCUS MAILS AWARENESS-RAISING MATERIALS ACROSS ITS THREE PROGRAM AREAS TO OVER 600,000 NATIONAL HOUSEHOLDS, WITH MESSAGES FOCUSING ON: RISK FACTORS AND SYMPTOM RECOGNITION THROUGH PUBLIC AWARENESS AND STEPS THE PUBLIC SHOULD TAKE THAT MAY HELP REDUCE THEIR RISK. LIFESTYLE CHOICES THAT PROMOTE GOOD HEALTH, ENCOURAGING READERS TO TAKE ACTION TO REDUCE THE LIKELIHOOD OF THE ONSET OF THE DISEASE. RESEARCH RESULTS AND TREATMENTS AVAILABLE TO ADDRESS THE DISEASE. BRIGHTFOCUS REGULARLY INTERACTS WITH ADVOCACY ORGANIZATIONS, GOVERNMENTS AT ALL LEVELS, AND MEMBERS OF THE MEDIA, TO CALL GREATER ATTENTION TO DISEASES OF MIND AND SIGHT AND SHARE THE LATEST RESEARCH AND BEST PRACTICES WITH PUBLIC FIGURES AND KEY STAKEHOLDERS. THROUGH OUR OWN OUTREACH EFFORTS, AS WELL AS VIA ACTIVE ROLES IN ADVOCACY COALITIONS, WE HELP ADVANCE THE CAUSE OF PIONEERING SCIENCE AND BETTER POSITION BRIGHTFOCUS AS A RESOURCE FOR THOSE STRUGGLING WITH AND SEARCHING FOR CURES FOR THESE TERRIBLE DISEASES. BRIGHTFOCUS IS THE PRESENTING SPONSOR OF THE HELEN KELLER PRIZE FOR VISION RESEARCH, ONE OF THE MOST PRESTIGIOUS RECOGNITIONS IN THE FIELD. SELECTED BY A PANEL OF THE WORLD'S FOREMOST VISION SCIENTISTS, EACH YEAR'S LAUREATE IS HONORED FOR A GROUNDBREAKING CONTRIBUTION OR DISCOVERY TO SAVE SIGHT. BRIGHTFOCUS BEGAN ITS SPONSORSHIP IN 2015 TO CALL GREATER ATTENTION TO VISION RESEARCH ACROSS THE PRIVATE AND PUBLIC SECTORS. BRIGHTFOCUS WAS HONORED IN 2023 FOR ITS CONTRIBUTIONS TO ADVANCING GLOBAL VISION RESEARCH BY THE ASSOCIATION FOR RESEARCH IN VISION AND OPHTHALMOLOGY (ARVO) FOUNDATION. FORM 990, PART III, LINE 4A, DESCRIPTION OF PROGRAM SERVICE: ALZHEIMER'S DISEASE RESEARCH (ADR) ALZHEIMER'S DISEASE IS THE ONLY CAUSE OF DEATH AMONG THE TOP 10 IN AMERICA WITHOUT A WAY TO PREVENT, CURE, OR EVEN SLOW ITS PROGRESSION. IT IS AN IRREVERSIBLE DEGENERATION OF THE BRAIN THAT CAUSES DISRUPTIONS IN MEMORY, COGNITION, PERSONALITY, AND OTHER FUNCTIONS AND INEVITABLY LEADS TO DEATH. AN ESTIMATED 55 MILLION PEOPLE WORLDWIDE HAVE ALZHEIMER'S DISEASE OR OTHER DEMENTIAS, WITH WOMEN AND BLACK AND HISPANIC ADULTS MOST AT RISK. ALZHEIMER'S DISEASE RESEARCH (ADR), A BRIGHTFOCUS FOUNDATION PROGRAM, FUNDS RESEARCH FOCUSED ON UNDERSTANDING THE CAUSES OF ALZHEIMER'S DISEASE, EARLY DETECTION, TREATMENTS TO HELP SLOW OR STOP ITS PROGRESSION, AND ULTIMATELY TO PREVENT THE DISEASE ALTOGETHER. ADR ANNUALLY AWARDS PEER-REVIEWED GRANTS TO SCIENTISTS FROM INSTITUTIONS WORLDWIDE WHO ARE CONDUCTING BIOMEDICAL AND CLINICAL RESEARCH ON ALZHEIMER'S DISEASE. SINCE INCEPTION, ADR HAS INVESTED NEARLY $190 MILLION IN RESEARCH GRANTS TO DEFEAT ALZHEIMER'S DISEASE. DURING THE FISCAL YEAR ENDING MARCH 31, 2025, ADR AWARDED $10,207,897 IN PEER-REVIEWED GRANT AWARDS TO 40 NEW RESEARCH PROJECTS. NOTABLE PROJECTS INCLUDE: INFLAMMATORY FACTORS DRIVING MYELIN DYSFUNCTION, NOVEL INTERVENTIONS USING FOCUSED ULTRASOUND TECHNOLOGY, HARNESSING DISEASE DIFFERENCES TO GENERATE PERSONALIZED PROTEIN SIGNATURES, THE ROLE OF MULTIPLE PREGNANCIES AND MENOPAUSE ON DEMENTIA RISK, AND DIFFERENCES IN GENETICS AND DISEASE RISK FOR UNDERREPRESENTED POPULATIONS. ADDITIONAL INFORMATION ABOUT SPECIFIC PROJECTS IS INCLUDED IN SCHEDULES F & I. BRIGHTFOCUS IS HONORED TO HAVE SUPPORTED THE EARLY RESEARCH OF TWO NOBEL PRIZE WINNERS. DR. STANLEY PRUSINER AND DR. PAUL GREENGARD, WHOSE WORK HAS BEEN INSTRUMENTAL IN OUR CURRENT UNDERSTANDING OF ALZHEIMER'S DISEASE. BRIGHTFOCUS CONTINUES ITS PARTNERSHIP WITH THE ACADEMIC JOURNAL MOLECULAR NEURODEGENERATION AS THE OFFICIAL JOURNAL OF BRIGHTFOCUS FOUNDATION. THE JOURNAL PUBLISHES TECHNICAL PAPERS RELATED TO NEURODEGENERATION IN THE THREE DISEASE AREAS. TO ACCELERATE SCIENTIFIC PROGRESS, IT IS AN OPEN-ACCESS JOURNAL, AND ALL CONTENT IS FREE OF CHARGE. THIS OPEN ACCESS ENSURES MAXIMAL REACH OF JOURNAL CONTENTS TO SCIENTISTS AND CARE PROVIDERS WORLDWIDE. MOLECULAR NEURODEGENERATION IS CURRENTLY THE HIGHEST IMPACT OPEN ACCESS JOURNAL IN THE NEUROSCIENCES. IN ADDITION TO SUPPORTING CUTTING-EDGE RESEARCH, ALZHEIMER'S DISEASE RESEARCH PROVIDES EXPERT-VETTED RESOURCES ON DETECTING, TREATING, AND LIVING WITH THE DISEASE. THESE ARE AVAILABLE ON OUR WEBSITE, WWW.BRIGHTFOCUS.ORG/ADR. FORM 990, PART III, LINE 4B, DESCRIPTION OF PROGRAM SERVICE: MACULAR DEGENERATION RESEARCH (MDR) AGE-RELATED MACULAR DEGENERATION IS A LEADING CAUSE OF VISION LOSS IN THE UNITED STATES. IT DESTROYS THE MACULA, THE PART OF THE EYE THAT PROVIDES SHARP, CENTRAL VISION NEEDED FOR SEEING OBJECTS CLEARLY. THE MOST COMMON EYE CONDITION IN PEOPLE AGE 60 AND OLDER, IT CAN LEAD TO VISION LOSS IN ONE OR BOTH EYES, MAKING IT DIFFICULT TO RECOGNIZE FACES, DRIVE A CAR, OR READ. AT LEAST 20 MILLION AMERICANS HAVE SOME TYPE OF MACULAR DEGENERATION, INCLUDING BOTH THE EARLY AND LATER STAGES OF THE WET AND DRY TYPES. MACULAR DEGENERATION RESEARCH (MDR), A BRIGHTFOCUS FOUNDATION PROGRAM, HAS AWARDED NEARLY $57 MILLION TO SCIENTISTS STUDYING THE DISEASE. THE LATEST RESEARCH IS FOCUSED ON NOVEL TREATMENTS, UNDERSTANDING THE CAUSES AND DISEASE PROGRESSION, PREDICTION METHODS AND DISEASE MODELING, DRUG THERAPIES, THE ROLE OF METABOLISM AND IMMUNE RESPONSE IN DISEASE RISK, GENES, AND NEW IMAGING, MACHINE LEARNING, AND SCREENING TECHNIQUES. MDR GRANTS ARE AVAILABLE TO MACULAR DEGENERATION RESEARCHERS WORLDWIDE. MDR PLACES SPECIAL EMPHASIS ON ENCOURAGING APPLICATIONS FROM YOUNG SCIENTISTS AND THOSE WITH CUTTING-EDGE IDEAS. ANNUAL GRANT APPLICATIONS ARE PEER-REVIEWED, AND RECIPIENT SELECTIONS ARE BASED ON SCIENTIFIC MERIT. DURING THE FISCAL YEAR ENDING MARCH 31, 2025, MDR AWARDED $3,774,565 IN PEER-REVIEWED GRANT AWARDS TO 12 NEW RESEARCH PROJECTS. DETAILS ABOUT SPECIFIC PROJECTS ARE INCLUDED IN SCHEDULES F & I. IN ADDITION TO SUPPORTING CUTTING-EDGE RESEARCH, MACULAR DEGENERATION RESEARCH PROVIDES EXPERT-VETTED RESOURCES ON DETECTING, TREATING, AND LIVING WITH THIS DISEASE. THESE ARE AVAILABLE ON OUR WEBSITE, WWW.BRIGHTFOCUS.ORG/MDR. FORM 990, PART III, LINE 4C, DESCRIPTION OF PROGRAM SERVICE: NATIONAL GLAUCOMA RESEARCH (NGR) GLAUCOMA IS THE SECOND LEADING CAUSE OF BLINDNESS WORLDWIDE ACCORDING TO A RECENT REPORT FROM THE WORLD HEALTH ORGANIZATION, APPROXIMATELY 80 MILLION PEOPLE AROUND THE WORLD HAVE GLAUCOMA. MORE THAN FOUR MILLION AMERICANS ARE LIVING WITH GLAUCOMA. IN THE UNITED STATES, GLAUCOMA IS A LEADING CAUSE OF BLINDNESS AMONG BLACK AND HISPANIC AMERICANS. WITH EARLY DETECTION AND TREATMENT, GLAUCOMA OFTEN CAN BE MANAGED TO PROTECT EYES FROM MORE SERIOUS VISION LOSS. IT IS ESTIMATED THAT ONLY HALF OF THE PEOPLE LIVING WITH GLAUCOMA ARE AWARE THAT THEY HAVE THE DISEASE. NATIONAL GLAUCOMA RESEARCH (NGR), A BRIGHTFOCUS FOUNDATION PROGRAM, HAS AWARDED NEARLY $53 MILLION WORLDWIDE IN RESEARCH GRANTS TOWARD THE STUDY OF GLAUCOMA. NGR-SUPPORTED RESEARCH HAS FOCUSED ON THE EYE-BRAIN CONNECTION, HOW PRESSURE BUILDUP IN THE EYE CAN AFFECT SYNAPTIC NERVE COMMUNICATIONS, NEUROPROTECTION AND OPTIC NERVE REGENERATION, DISCOVERING GLAUCOMA RISK GENES, AI/DEEP LEARNING AND ADAPTIVE OPTICS, SLEEP DISTURBANCE AND GLAUCOMA RISK, DEVELOPING EARLY GLAUCOMA SCREENING, AND PURSUING NOVEL GENETIC COUNSELING AND COMMUNICATION STRATEGIES, AMONGST OTHER INNOVATIVE PURSUITS. NGR GRANTS ARE AVAILABLE TO GLAUCOMA RESEARCHERS WORLDWIDE. NGR PLACES SPECIAL EMPHASIS ON ENCOURAGING APPLICATIONS FROM YOUNG SCIENTISTS AND THOSE WITH CUTTING-EDGE IDEAS. ANNUAL GRANT APPLICATIONS ARE PEER-REVIEWED, AND RECIPIENT SELECTIONS ARE BASED ON SCIENTIFIC MERIT. DURING THE FISCAL YEAR ENDING MARCH 31, 2025, NGR AWARDED $1,818,979 IN PEER-REVIEWED GRANT AWARDS FOR 10 NEW PROJECTS. DETAILS ABOUT SPECIFIC PROJECTS ARE INCLUDED IN SCHEDULES F & I. IN ADDITION TO SUPPORTING CUTTING-EDGE RESEARCH, NATIONAL GLAUCOMA RESEARCH PROVIDES EXPERT-VETTED RESOURCES ON DETECTING, TREATING, AND LIVING WITH THE DISEASE. THESE ARE AVAILABLE ON OUR WEBSITE, WWW.BRIGHTFOCUS.ORG/NGR. FORM 990, PART VI, SECTION B, LINE 11B A DRAFT OF THE FEDERAL FORM 990 IS DISTRIBUTED TO THE AUDIT COMMITTEE FOR REVIEW PRIOR TO BEING SUBMITTED TO THE INTERNAL REVENUE SERVICE. THE DRAFT FEDERAL FORM 990 IS DISTRIBUTED EARLY ENOUGH TO PROVIDE EACH COMMITTEE MEMBER WITH A REASONABLE AMOUNT OF TIME FOR REVIEW AND SUBMISSION OF QUESTIONS OR COMMENTS PRIOR TO THE FILING DEADLINE. THE FINAL FEDERAL FORM 990 IS DISTRIBUTED TO EACH MEMBER OF THE FULL BOARD OF DIRECTORS PRIOR TO BEING FILED WITH THE INTERNAL REVENUE SERVICE. THE DRAFT OR FINAL FEDERAL FORM 990 MAY BE DISTRIBUTED IN PERSON, BY REGULAR MAIL, E-MAIL, OR FAX. FORM 990, PART VI, SECTION B, LINE 12C BRIGHTFOCUS HAS ALL EMPLOYEES, OFFICERS, AND DIRECTORS AGREE TO THE CODE OF CONDUCT THAT INCLUDES ADHERENCE TO THE CONFLICT OF INTEREST AND IMPLEMENTATION POLICY. EACH BOARD DIRECTOR, OFFICER, AND EMPLOYEE IS REQUIRED TO COMPLETE A CONFLICT OF INTEREST DISCLOSURE STATEMENT ANNUALLY. EMPLOYEES MEET ANNUALLY WITH THE BRIGHTFOCUS' CHIEF COMPLIANCE OFFICER TO REVIEW THEIR CONFLICT OF INTEREST STATEMENTS, AND GIVE AN ANNUAL CONFLICT OF INTEREST COMPLIANCE REPORT TO THE BOARD CHAIR AND VICE CHAIR. IF A CONFLICT IS REPORTED, IT IS THEN REFERRED TO THE PRESIDENT/CEO AND/OR BRIGHTFOCUS' LEGAL COUNSEL AND, IF APPROPRIATE AND NECESSARY, THEN TO THE BOARD OF DIRECTORS OR ITS APPOINTED COMMITTEE FOR FURTHER ACTION. THE DIRECTOR'S AND OFFICER'S STATEMENTS ARE REVIEWED BY THE BRIGHTFOCUS LEGAL COUNSEL. IF A CONFLICT IS REPORTED, IT IS THEN REFERRED TO THE BOARD OF DIRECTORS OR ITS APPOINTED COMMITTEE FOR FURTHER ACTION. AT THE TIME OF THE BRIGHTFOCUS DISCUSSION AND DECISION CONCERNING A CONFLICT OF INTEREST, THE CONFLICTED PARTY IS NOT PRESENT IN THE MEETING. FORM 990, PART VI, SECTION B, LINE 15 BRIGHTFOCUS' BOARD OF DIRECTORS HAS OVERALL AUTHORITY AND RESPONSIBILITY FOR APPROVING THE ANNUAL BUDGET WHICH INCLUDES SALARY AND BENEFITS FOR ALL EMPLOYEES AT EVERY LEVEL INCLUDING NON-DIRECTOR OFFICERS AND KEY EMPLOYEES. ALL PAY ADJUSTMENTS ARE MADE ON A YEARLY BASIS EFFECTIVE APRIL 1ST, THE BEGINNING OF THE BRIGHTFOCUS FISCAL YEAR. BEFORE APPROVING THE COMPENSATION OF THE PRESIDENT/CEO, THE BOARD DETERMINES THE TOTAL COMPENSATION TO BE PROVIDED BY BRIGHTFOCUS TO THE PRESIDENT/CEO IS REASONABLE CONSIDERING THE POSITION, RESPONSIBILITY AND QUALIFICATION OF THE POSITION HELD, INCLUDING THE RESULT OF AN EVALUATION OF PRIOR PERFORMANCE FOR BRIGHTFOCUS, IF APPLICABLE. THE PRESIDENT/CEO IS EVALUATED YEARLY BY THE BOARD OF DIRECTORS USING AN IN-DEPTH GOAL ATTAINMENT STRUCTURE, THAT INCLUDES A SELF-ASSESSMENT AND A BOARD OF DIRECTOR'S ASSESSMENT AND EVALUATION AGAINST SET GOALS, OUTCOMES, AND DELIVERABLES. IN ADDITION, THE BOARD OF DIRECTORS PERIODICALLY ENGAGES AN OUTSIDE CONSULTANT TO OBTAIN AND CONSIDER APPROPRIATE DATA, INCLUDING A SALARY SURVEY, WHICH INCLUDES INFORMATION COMPILED FROM THE FEDERAL FORM 990 OF OTHER ORGANIZATIONS, CONCERNING COMPENSATION PAID TO CEOS IN SIMILAR CIRCUMSTANCES. IN MAKING THE DETERMINATION, THE BOARD OF DIRECTORS CONSIDERS TOTAL COMPENSATION TO INCLUDE THE SALARY AND VALUE OF ALL BENEFITS PROVIDED BY BRIGHTFOCUS TO THE INDIVIDUAL IN PAYMENT FOR SERVICES. AT THE TIME OF THE BRIGHTFOCUS BOARD DISCUSSION AND DECISION CONCERNING THE PRESIDENT/CEO'S COMPENSATION, THE PRESIDENT/CEO IS NOT PRESENT IN THE MEETING. THE BOARD OF DIRECTORS SHALL SET FORTH THE BASIS FOR ITS DECISIONS WITH RESPECT TO COMPENSATION IN THE MINUTES OF THE MEETING AT WHICH THE DECISIONS ARE MADE, INCLUDING THE CONCLUSIONS OF THE EVALUATION AND THE BASIS FOR DETERMINING THAT THE INDIVIDUAL'S COMPENSATION WAS REASONABLE CONSIDERING THE EVALUATION AND COMPARABILITY DATA. THE PRESIDENT/CEO IS CHARGED WITH SETTING THE SALARIES OF ALL OTHER EMPLOYEES IN ACCORDANCE WITH A COMPENSATION STRUCTURE AND BUDGET APPROVED BY THE BOARD OF DIRECTORS. THE PRESIDENT/CEO AND HUMAN RESOURCES REVIEW EMPLOYEE COMPENSATION AND BENEFITS THAT INCLUDE KEY EMPLOYEES, BY PERIODICALLY ENGAGING AN OUTSIDE CONSULTANT TO CONDUCT COMPENSATION AND BENEFIT BENCHMARKING STUDIES THAT INCLUDE VARIOUS REGIONAL AND NATIONAL NON-PROFIT COMPENSATION REPORTS AND SURVEYS. COMPENSATION DELIBERATIONS AND DECISIONS INCLUDE THE REVIEW OF SELF AND SUPERVISORY EVALUATIONS OF EMPLOYEE PERFORMANCE COMPARED TO SET INDIVIDUAL AND ORGANIZATIONAL GOALS. FORM 990, PART VI, SECTION C, LINE 19 BRIGHTFOCUS MAKES ITS GOVERNING DOCUMENTS INCLUDING ITS ARTICLES OF INCORPORATION AND BYLAWS, THE FEDERAL FORM 1023, THE 501(C)(3) LETTER OF DETERMINATION FROM THE INTERNAL REVENUE SERVICE, CONFLICT OF INTEREST POLICY, AUDITED FINANCIAL STATEMENTS AND FEDERAL FORM 990 AVAILABLE TO THE PUBLIC UPON REQUEST. IN ADDITION, THE PUBLIC ALSO HAS ACCESS TO THE ANNUAL REPORT, AUDITED FINANCIAL STATEMENTS, THE 501(C)(3) LETTER OF DETERMINATION FROM THE INTERNAL REVENUE SERVICE, AND FEDERAL FORM 990 ON ITS WEBSITE AT WWW.BRIGHTFOCUS.ORG. FORM 990, PART XI, LINE 9: RECOVERIES OF PRIOR YEAR GRANTS 105,727. CHANGE IN PRESENT VALUE OF GRANTS 4,590. FORM 990, PART XII, LINE 2C: THE PROCESS HAS NOT CHANGED FROM PRIOR YEAR. NATIONAL DEVELOPMENT LLC 22512 GATEWAY CENTER DRIVE CLARKSBURG MD 20871 237337229 PROPERTY RENTAL AND MANAGEMENT MD 8684432 24681 BRIGHTFOCUS FOUNDATION AMERICAN HEALTH ASSISTANCE LLC 22512 GATEWAY CENTER DRIVE CLARKSBURG MD 20871 237337229 OWNER OF BRIGHTFOCUS HEADQUARTERS MD 0 2981266 BRIGHTFOCUS FOUNDATION