R01AG073439

Sex-Specific Genetic Drivers of Alzheimer's Disease Endophenotypes - Abstract

As the population ages, late-onset Alzheimer's disease (AD) is becoming an increasingly important public health issue. AD disproportionately affects women. Of the more than 5 million people in the United States afflicted with this disease, two-thirds are women. Women with AD have more neuropathology than men with AD, have more severe cognitive symptoms, and more severe neurodegeneration, suggesting that the disease affects male and female brains in different ways. Thus, a focus on sex differences in AD is essential to move the field towards effective interventions.

The identification of sex-specific genetic drivers of AD and AD-related endophenotypes could transform the way treatments are administered and be a critical step towards personalized interventions for AD. Research from both our group and others has begun to uncover genetic factors that explain some of the observed differences between males and females, specifically in terms of AD neuropathology and cognitive decline. To advance the field, additional genetic effects must be discovered and the underlying mechanisms of sex-specific pathways of injury must be examined.

The objective of this project is to identify and replicate genetic effects that act in a sex-specific manner to drive the neuropathological presentation and clinical progression of AD. The present proposal will advance our understanding of sex-specific genetic contributors to AD endophenotypes by leveraging data from 30 studies of aging and AD (N=33,740) to assess genetic associations with AD neuropathology and cognitive decline. The outcome of this project will highlight new candidate pathways and begin the process of characterizing the mechanisms by which genetic variation among males and females affects the risk and clinical symptoms of AD.

The sex-specific pathways identified will offer therapeutic targets and help move the field towards personalized interventions that consider an individual's sex and neuropathological presentation.

Vanderbilt University Medical Center

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]

Nashville, Tennessee 372152691 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 347% from $910,643 to $4,067,887.