U19AG074879

Centrally-Linked Longitudinal Peripheral Biomarkers of AD in Multi-Ethnic Populations - Summary Abstract (30 lines):

Existing cerebrospinal fluid (CSF) and neuroimaging measures of amyloid SS, tau and neurodegeneration (A,T,N) serve as useful diagnostic biomarkers for Alzheimer's disease (AD), however there remains an urgent, unmet need for blood-based biomarkers in AD.

First, multi-omic studies discovered many perturbed biological pathways in AD, however, systematic studies for biomarkers that capture these diverse biological facets of AD are limited.

Second, AD is a heterogeneous disorder but biomarkers that can distinguish the biological subtypes of AD are lacking.

Third, core AD neuropathology often co-exists with other neuropathologies such as vascular disease (V). These co-morbidities and co-pathologies need to be considered in biomarker discovery.

Fourth, existing biomarker studies are heavily focused on non-Hispanic whites (NHW). Similar studies in underrepresented populations (URP) are needed.

This U19, bringing together >40 experts across 13 institutions, aims to bridge these knowledge gaps for discovery and validation of centrally-linked longitudinal peripheral biomarkers of AD (CLEAR-AD) in multi-ethnic populations.

CLEAR-AD U19 is based on the premise that AD is a complex disorder in which many biological pathways are disrupted due to multi-omic perturbations, which can be detected in the brain and reflected in blood, i.e. centrally-linked peripheral molecular signatures (CLPMS).

The specific aims of CLEAR-AD U19 are:

1) To discover CLPMS of the complex and heterogeneous AD pathophysiology and its co-pathologies.

2) To identify longitudinal CLPMS that detect and predict dynamic neuroimaging, fluid biomarker, and clinical changes across AD spectrum.

3) To characterize differences and similarities in CLPMS profiles across NHW, African American (AA) and Latino American (LA) participants to uncover biomarker patterns in multi-ethnic groups.

4) To make these vast resources available to the scientific community to amplify and accelerate its impact.

In this U19 managed by the Administrative Core, we will leverage NIH-funded ADNI, MCSA and ADRC cohorts of >3,700 multi-ethnic participants to generate >20,000 multi-omics measures (Omics Core) that will be processed and integrated with >48,000 harmonized AD cognitive, neuroimaging and fluid endophenotypes (Analytic Core).

Using these data, we will identify brain region and cell-type specific CLPMS, which reflect biological subtypes of AD and disease stage (Project 1).

We will discover longitudinal changes in CLPMS that predict cognitive and A/T/N/V progression (Project 2).

We will define longitudinal cognitive and A/T/N/V changes and CLPMS in URP that are either conserved with NHW or population-specific (Project 3).

This U19 will a) identify the next generation of AD biomarkers with mechanistic insights; b) establish a precision medicine approach for rigorous multi-omics biomarker discovery and validation in AD; c) discover molecules that can serve as biomarkers and therapeutic targets; d) enhance biomarker research in trial-ready multi-ethnic populations; and e) generate and share a vast and harmonized resource of endophenotype and multi-omics data in NIH-funded cohorts.

Mayo Clinic Jacksonville (A Nonprofit Corporation)

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]

Jacksonville, Florida 322241865 United States

Single Zip Code

Complex Integrated Multi-Component Projects in Aging Research (U19 Clinical Trial Optional) (PAR-19-374)

Amendment Since initial award the total obligations have increased 56% from $16,496,676 to $25,697,045.