# Predictive Metabolite Signature for Alzheimer's Disease - a Nested Case-Control Study

> **NIH NIH P01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $421,857

## Abstract

Project Summary/Abstract
Alzheimer’s Disease (AD) is the leading cause of for cognitive impairment and dementia among older adults in
the U.S. Further, evidence suggests there is a strong association between cognitive dementia vascular disease
and regardless of subtype, with vascular pathology estimated to contribute to at least half of all diagnosed
dementia cases. In the absence of curative treatments it is critical to identify high risk individuals and determine
efficacious targets for interventions to slow or arrest progression as early as possible. Within the context of this
background, we propose to expand the scope of the Einstein Aging Study (EAS) by utilizing biorepository
samples to measure serum metabolite concentrations and combine these data with existing EAS longitudinal
measures of vascular disease risk to determine their predictive value and identify individuals at risk for incident
AD. The EAS is a well characterized community based cohort of adults aged ≥70 years in Bronx County, NY.
Metabolomics is an emerging field that shows great promise in identifying biomarkers associated with
preclinical abnormalities and subsequent onset of clinical outcomes. The overarching aim of the proposed work
is to identify serum metabolites/metabolic signatures that will predict the onset of AD with the ultimate goal of
facilitating the development of early intervention strategies to prevent or slow progression. Proposed is a
nested case-control study of 90 incident cases who developed AD at least 2-years post EAS enrollment and 90
cognitively normal controls, who remained free of dementia during follow-up, matched for sex, age, education,
race/ethnicity and length of follow-up. We will measure serum metabolite concentrations at two time points;
study entry (baseline) and time of AD diagnosis, using a combination of untargeted and targeted
methodologies. Metabolite panels will include primary metabolites (carbohydrates and sugar phosphates,
amino acids, hydroxyl acids, purines, pyrimidines, aromatics, fatty acids); biogenic amines (trimethylamine-N-
oxide, s-adenosyl methionine, s-adenosyl homocysteine, nucleotides and nucleosides, methylated and
acetylated amines, dipeptides and oligopeptides); and complex lipids (acyl carnitines, ceramides,
sphingolipids, phospholipids; non-cholesterol sterols). We will then determine whether change in serum
metabolite concentrations or metabolite signatures between baseline and time of AD diagnosis will discriminate
between AD cases and cognitively normal controls. For those metabolites that appear to be candidate
biomarkers on the basis of this change we will then determine whether these serum metabolite concentrations
or metabolite signatures measured in the baseline samples are significantly different between cases and
controls, and whether already available cardiometabolic risk factor data improves the predictive capacity of the
measures. Combining these new measures with the rich EAS dataset provides a un...

## Key facts

- **NIH application ID:** 9937199
- **Project number:** 3P01AG003949-37S1
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Richard B. LIPTON
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $421,857
- **Award type:** 3
- **Project period:** 1982-09-29 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9937199

## Citation

> US National Institutes of Health, RePORTER application 9937199, Predictive Metabolite Signature for Alzheimer's Disease - a Nested Case-Control Study (3P01AG003949-37S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9937199. Licensed CC0.

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