RF1AG096165

BIOLOGICAL DRIVERS OF SEX DIFFERENCES IN FRONTOTEMPORAL DEMENTIA - ABSTRACT DEMENTIA PREVALENCE AND DISEASE COURSE DIFFERS BY SEX. YET, DESPITE BEING THE LEADING CAUSE OF YOUNG ONSET DEMENTIA, VERY LITTLE IS KNOWN ABOUT SEX DIFFERENCES IN FRONTOTEMPORAL DEMENTIA (FTD). OUR ACCUMULATING DATA SUGGEST FEMALES WITH FTD SHOW PATTERNS OF “COGNITIVE RESILIENCE” CONSISTENT WITH DELAYED SYMPTOM MANIFESTATION, DESPITE HIGHER NEURODEGENERATIVE BURDEN. WE HYPOTHESIZE THAT FEMALE-SPECIFIC BIOLOGY DRIVES THE UNIQUE CLINICAL COURSE OF WOMEN SUFFERING FROM FTD. OUR OVERARCHING GOAL IS TO DEEPLY CHARACTERIZE UNDERSTUDIED FEMALE BIOLOGY TO UNLOCK NEW INSIGHTS INTO FTD PATHOPHYSIOLOGY, PRECISION TREATMENTS, AND NOVEL DEMENTIA RISK AND RESILIENCE TARGETS FOR ALL BRAINS. TO DO SO, OUR PROPOSAL WILL LEVERAGE TWO DEEPLY PHENOTYPED, LONGITUDINALLY-FOLLOWED LOCAL AND INTERNATIONAL COHORTS OF GENETIC AND SPORADIC FORMS OF FTD AND HEALTHY CONTROLS (N=1095). WE WILL BE THE FIRST COMPREHENSIVE EVALUATION OF BIOLOGICAL SEX DIFFERENCES IN FTD. OUR AIMS WILL: 1) PROSPECTIVELY ASSAY LONGITUDINAL SEX HORMONE LEVELS IN PLASMA (E.G.,17𝛽-ESTRADIOL, TESTOSTERONE, PROGESTERONE), 2) IDENTIFY SEX-SPECIFIC PROTEOMIC SIGNATURES OF FTD FROM CEREBROSPINAL FLUID AND PLASMA, 3) COLLECT A NEW FEMALE REPRODUCTIVE HEALTH HISTORY MEASURE (E.G., AGE OF MENOPAUSE, PREGNANCIES), AND 4) DEVELOP DISEASE PROGRESSION MODELS THAT INCORPORATE SEX-SPECIFIC FACTORS TO PRECISELY PROGNOSTICATE FTD TRAJECTORIES IN MALES AND FEMALES. THIS PROPOSAL CONTRIBUTES TO A HIGH PRIORITY, UNDERSERVED SCIENTIFIC AREA. FOR INSTANCE, AMONG NEUROIMAGING PAPERS PUBLISHED SINCE THE 1990S, <0.5% CONSIDER FACTORS SPECIFIC TO THE FEMALE BODY. THIS KNOWLEDGE GAP CREATES TREATMENT INEQUITIES AS EVIDENCED BY THE CURRENTLY AVAILABLE THERAPY FOR ALZHEIMER’S DISEASE (LECANEMAB), WHICH SHOWS LESS THAN HALF THE EFFICACY IN FEMALES COMPARED TO MALES. OUR PROPOSAL WILL THEREFORE ADDRESS A MAJOR HEALTH DISPARITY, ADVANCE PRECISION APPROACHES TO FTD BEFORE TREATMENT INEQUITIES ARISE, AND LEVERAGE OVERLOOKED FEMALE BIOLOGY TO DISCOVER NEW INSIGHTS INTO DEMENTIA PREVENTION TARGETS RELEVANT FOR ALL BRAINS.

San Francisco Regents Of The University Of California

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

San Francisco, California 94143 United States

Single Zip Code

Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01 Clinical Trial Optional) (PAR-22-093)