U01AG088562

The role of chemical exposures in Alzheimer's disease (AD) and its trajectory - It has become increasingly clear that environmental exposures, the genome, gut microbiome, diet, and lifestyle all affect an individual’s metabolic state contributing to brain health and disease, including Alzheimer’s disease (AD) and AD-related dementia (ADRDS).

Our AD Metabolomics Consortium (ADMC), in collaboration with the AD Neuroimaging Initiative (ADNI), is applying state-of-the-art metabolomics and lipidomics technologies combined with genomic and imaging data to map metabolic failures across the spectrum and trajectory of AD-ADRDS.

The ADMC is part of the Accelerating Medicines Partnership for AD (AMP-AD), a flagship precompetitive partnership that brings government, industry, and nonprofit organizations together to transform the current model for developing new AD diagnostics and treatments.

Our work confirmed that peripheral metabolic changes, influenced by the exposome, inform about cognitive and brain imaging changes and ATN markers for disease, highlighting peripheral and central changes are connected in part, through the metabolome.

The Alzheimer Gut Microbiome Project (AGMP) that we launched in partnership with ten AD Research Centers (ADRC) and large diet and lifestyle interventions (POINTER, MIND, BEAT-AD) aims to define the influences of the gut microbiome, diet, and gut-brain axis in AD.

This research infrastructure is building the first AD molecular atlas that captures exposome influences on AD-associated metabolomic profiles.

Five metabolomic centers of excellence are completing a ring trial to identify environmental chemical exposures, dietary components, and drug signatures that when linked to gut microbiome and metabolomic data will define exposome profiles associated with AD/ADRDS.

In this U01, we leverage a large NIA-funded collaborative infrastructure, connections to 10 ADRCs, and access to unique community-based longitudinal cohort studies and biobanks (FHS, ROSMAP, Rotterdam, UK Biobank) to: (I) expand coverage of the chemical exposome in blood and brain, and (II) link identified signatures to brain aging, incident dementia, and AD.

Human data generated in this project will inform and be informed by results from complementary preclinical exposome studies in AD mouse models (AG-24-023) and cell-based systems (AG-24-241).

A long-standing partnership with Sage Bionetworks allows for rapid sharing of exposome data collected under this application through the AD Knowledge Portal.

We will leverage data generated under the AMP-AD, AGMP, and this U01 to enable data harmonization with existing data generated in the AMP-AD and AGMP with the goal of integrating of complex exposure data across multiple cohorts.

This project provides an unparalleled opportunity to create a deeper understanding of how the exposome interacts with genetics, gut microbiome, and metabolome to modulate AD pathogenesis, potentially leading to novel therapeutic approaches and preventative measures for AD that address ethnic, socioeconomic, and geographic diversity.

Our European and USA partners connect us with large exposome initiatives including in the Netherlands and “The Human Health Exposure Analysis Resource” (HHEAR) network.

Duke University

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]

Durham, North Carolina 277053976 United States

Single Zip Code

Quantifying the Impact of Environmental Toxicants on Alzheimer's Disease (AD) and AD-Related Dementias (ADRD) Risk in Cohort Studies (U01 Clinical Trial Not Allowed) (RFA-AG-24-022)

Amendment Since initial award the total obligations have increased 84% from $2,499,382 to $4,606,607.