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

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $2,730,089

## Abstract

ABSTRACT. The analysis of cerebrospinal fluid (CSF) and molecular PET biomarkers of Aβ and phospho-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) that was intended to add precision to the diagnosis for clinical
purposes, therapeutic trials and regulatory agencies. For observational epidemiological research the widespread
use of these types of biomarkers is not possible because of the expense and limited access to cyclotrons
necessary for molecular imaging and the difficulty in obtaining CSF in large studies. Further, it is clear that the
relationship of biomarker values to clinical diagnoses can also 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 (Aβ40, Aβ42, p-tau217, neurofilament light chain or NFL) combined with
brain MRI provides an opportunity to investigate the application of “A/T/N biomarker profile” in community-based,
observational study, and 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 neurofilament
light [NfL], and MRI (brain volumes and cortical thickness) will be assessed in a longitudinal, multi-ethnic
community-based elderly cohort (24% white non-Hispanic, 28% African American, 48% Caribbean Hispanic).
The cohort has been genetically characterized, and has stored DNA, sera, and plasma. The effects of
cerebrovascular disease “V” and psychosocial factors will also be investigated as potential modulators of the
“A/T/N biomarker profile”. We will use publicly available genetic data in African American, Caribbean Hispanic
and non-Hispanic white participants that included the WHICAP cohort to create ethnic-specific polygenic risk
scores (ePRS). This will allow the identification of variants associated with the endophenotypes underlying the
“A/T/N biomarker profile” and augment the ePRS association with the clinical diagnoses of AD.
We will maintain longitudinal follow-up of the WHICAP cohort, adding participants only to account for attrition,
collecting whole blood for plasma and sera, ascertaining psychosocial and biomedical risk and protective factors
and obtaining structural MRI measures 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)...

## Key facts

- **NIH application ID:** 10214302
- **Project number:** 1R01AG072474-01
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** ADAM M BRICKMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,730,089
- **Award type:** 1
- **Project period:** 2021-06-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214302

## Citation

> US National Institutes of Health, RePORTER application 10214302, Epidemiological and Genetic Investigations of Blood-Based Biomarkers for Alzheimer's Disease in the Multiethnic, Washington Heights, Inwood, Columbia Aging Project (WHICAP) (1R01AG072474-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10214302. Licensed CC0.

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