R01AG082056

Social epigenetics of Alzheimer's disease and related dementias in Latin American countries - project summary (abstract)

Alzheimer’s disease (AD) and related dementias like frontotemporal dementia (FTD) disproportionately affect Latinos and socioeconomically disadvantaged groups. Nevertheless, the bulk of the research exploring the multifaceted biology of dementia, which includes both genetic and epigenetic aspects, has predominantly been focused on Caucasian populations and higher-income countries (HICs).

To address these disparities and expand dementia research in Latin America countries (LAC) and low-income countries, our group has established the NIH-NIA/TAU Consortium/Alzheimer Association funded multi-partner consortium to expand dementia research in Latin America (REDLAT) cohort study of Latinos with AD, FTD, and healthy controls.

REDLAT represents a first-in-class dataset of Latinos with AD, FTD, and demographically matched healthy controls consisting of biospecimen collection, standardized clinical, neuropsychological, genomic, neuroimaging, and SDH data, which our research group has utilized to identify unique combinations of environmental and genetic factors of dementia in Latin American countries (LAC).

Our preliminary epigenetic data reveals shared and distinct epigenetic DNA methylation differences related to AD and FTD, including a "Hispanic paradox" with epigenetic biomarkers underestimating biological aging in Latinos despite AD and FTD diagnoses. Moreover, our preliminary data harnessing matched SDH data from REDLAT suggests a link between altered DNAm states of inflammatory, stress, and cardiometabolic genes and socioeconomic status.

Our overall hypothesis is that a social adversity-epigenetic signature in immune cells at regulatory regions of proinflammatory, stress, and cardiometabolic genes associates with dementia presentation and heterogeneity in Latinos.

In this proposal, we test this overall hypothesis and add epigenetic DNAm data to the REDLAT cohort by (1) leveraging existing blood biospecimens from 1,600 participants (N=400 AD, N=400 FTD, N=800 controls) with different social determinants of health (SDH) levels, including a low-middle income country (Colombia), an upper middle-income country (Argentina), and HICs countries (Chile and the US) and (2) leverage existing ongoing rolling REDLAT recruitment to add an out-of-sample validation epigenetic dataset of 400 additional participants (N=100 AD, N=100 FTD, and N=200 controls) to generate an epigenetic dataset from 2,000 total Latinos in REDLAT.

With these rich epigenetic data, we will identify shared and distinguishing epigenetic DNAm features associated with AD and FTD presentation in Latinos. Moreover, we will utilize this extensive epigenetic dataset to better understand the interactions between specific SDH factors and distinct epigenetic changes in the genome.

Understanding dementia presentation through the lens of epigenetics and SDH in Latinos across diverse regions of LAC and the US will advance regionally-informed novel strategies to address dementia disparities by paving the way for targeted interventions and prevention strategies that take into account both epigenetic and SDH factors.

San Diego 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]

La Jolla, California 92093 United States

Single Zip Code

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

Amendment Since initial award the total obligations have increased 203% from $1,199,134 to $3,637,245.