R01AG074341

Molecular diversity among hippocampal and entorhinal cells in aging and Alzheimer's disease - Abstract

Alzheimer’s disease (AD) is the leading cause of dementia (60-80%), affecting tens of millions of people globally and, due to longer lifespans and aging populations, perhaps hundreds of millions more by 2050.

AD pathology is first observed in allocortical and limbic areas within the cerebrum, in particular medial temporal cortical regions critical for learning and memory including the hippocampal formation and entorhinal cortex (HIP-EC).

Within these areas, pathology exhibits subregional and cell type specificity, with layer 2 of entorhinal cortex and the hippocampal CA1 field (Sommer’s sector) exhibiting pathological hallmarks before dentate gyrus granule cells and other major hippocampal neuronal subtypes.

Understanding the molecular basis of this selective vulnerability (and conversely the resilience of other cell types) will provide new insights into the etiology of AD, but to date only limited efforts have been made to understand the molecular signatures differentiating neuronal and non-neuronal cells in HIP-EC.

We therefore propose to conduct single nuclear RNA sequencing (snRNA-seq) and single nuclear assay for transposase accessible chromatin (snATAC-seq) in 5 regions of HIP-EC of AD brains, young/mid adult and aged neurotypical “control” human brains, and young adult and aged rhesus macaque brains.

This will allow us to develop a high resolution cell census of HIP-EC which will in turn allow us to identify enriched genes, gene expression patterns, gene regulatory networks, and biological processes potentially mediating cell type specific differences in the AD and aged HIP-EC.

Yale Univ

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]

New Haven, Connecticut 065103210 United States

Single Zip Code

Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01 Clinical Trial Optional) (PAR-19-070)

Amendment Since initial award the total obligations have increased 115% from $1,589,662 to $3,417,912.