R01AG072474

Epidemiological and Genetic Investigations of Blood-Based Biomarkers for Alzheimer's Disease in the Multiethnic, Washington Heights, Inwood, Columbia Aging Project (WHICAP) - Abstract

The analysis of cerebrospinal fluid (CSF) and molecular PET biomarkers of amyloid beta (Aβ) plaques and phosphorylated tau (p-tau) combined with MRI assessment of global and regional neurodegeneration led to the development of the "A/T/N" classification scheme for Alzheimer's disease (AD). This classification scheme was intended to add precision to the diagnosis for clinical purposes, therapeutic trials, and regulatory agencies.

However, for observational epidemiological research, the widespread use of these types of biomarkers is not possible due to the expense and limited access to cyclotrons necessary for molecular imaging, as well as the difficulty in obtaining CSF in large studies. Additionally, it is clear that the relationship of biomarker values to clinical diagnoses can differ by age, sex, and race/ethnic group, and few studies have included diverse cohorts representative of the population in the US.

The advent of newly established blood-based biomarkers, such as Aβ40, Aβ42, p-tau217, and neurofilament light chain (NFL), combined with brain MRI, provides an opportunity to investigate the application of the "A/T/N biomarker profile" in a community-based, observational study. This study aims to create endophenotypes that can be used to identify genetic susceptibility. The Washington Heights, Inwood Columbia Aging Project (WHICAP) study is one of the few cohorts where the newly established blood-based biomarkers and well-established neuroimaging biomarkers for AD can be used to investigate a blood-based "A/T/N biomarker profile" across race/ethnic groups and by age and sex.

Amyloid (plasma Aβ40 and Aβ42), tau (plasma total tau and p-tau217), and neurodegeneration (plasma NFL) will be assessed, along with MRI measures of brain volumes and cortical thickness, in a longitudinal, multi-ethnic community-based elderly cohort. The cohort consists of 24% white non-Hispanic, 28% African American, and 48% Caribbean Hispanic participants. This cohort has been genetically characterized, and DNA, sera, and plasma samples have been stored.

The effects of cerebrovascular disease and psychosocial factors will also be investigated as potential modulators of the "A/T/N biomarker profile". The study will utilize publicly available genetic data in African American, Caribbean Hispanic, and non-Hispanic white participants, including the WHICAP cohort, to create ethnic-specific polygenic risk scores (PRS). This will allow the identification of variants associated with the endophenotypes underlying the "A/T/N biomarker profile" and augment the PRS association with the clinical diagnoses of AD.

The WHICAP cohort will be longitudinally followed up, with additional participants added only to account for attrition. Whole blood samples will be collected for plasma and sera, and psychosocial and biomedical risk and protective factors will be ascertained. Structural MRI measures will be obtained at least twice in participants over a four-year period.

The overall goals of this project are to:
1) Investigate variability in blood-based biomarkers and MRI measures in the "A/T/N biomarker profile" as it applies to clinical diagnoses in a multi-ethnic cohort.
2) Investigate blood-based biomarkers as endophenotypes in genetic analyses for earlier detection and diagnosis of AD.
3) Investigate how cerebrovascular disease and psychosocial factors modulate the use of blood-based and MRI biomarkers.

The Trustees Of Columbia University In The City Of New York

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 York, New York 10032 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 388% from $2,730,089 to $13,310,071.