# Metabolomic Signatures for Disease Sub-classification and Target Prioritization in AMP-AD

> **NIH NIH U01** · DUKE UNIVERSITY · 2021 · $1,619,858

## Abstract

ABSTRACT:
The AMP-AD Target Discovery and Preclinical Validation Project aims to reduce the time between the discovery
of potential drug targets and the development of new drugs for Alzheimer’s disease (AD) treatment and
prevention (RFA-AG-18-013). The six involved consortia under AMP-AD have generated large-scale molecular
data from human brain samples with network modeling approaches and experimental validation that defined
novel potential drug targets for AD. A major challenge for the next phase is to provide a deeper molecular
understanding of key implicated pathways and their enzymes, transporters and signaling molecules that are
amenable for drug discovery efforts. Defining a molecular basis for heterogeneity within disease is critical for
successful drug development within a precision medicine context. Our AD Metabolomics Consortium (ADMC)
became part of AMP-AD one-year post inception of Phase I, adding the power of metabolomics to these efforts.
AD has foundational metabolic changes that happen early and pre-symptomatically. Most of the genes
implicated in AD suggest a role for lipid processing, immune function regulation, and phagocytosis that are all
related to metabolic functions. Detailed biochemical knowledge advanced the medical field, providing tools for
monitoring disease, such as measures of glucose and cholesterol in diabetes and cardiovascular diseases,
and resulted in development of drugs, such as statins and antidepressants. In Phase I, we helped to define
biochemical trajectories of disease bridging peripheral and brain metabolic changes to AMP-AD. We built
metabolic networks for early changes in AD that correlate with CSF and brain imaging changes, defining sex
differences and their biochemical trajectories of disease, identifying the role of the gut microbiome and liver in
cognitive decline and brain glucose changes and atrophy, supporting the importance of the gut-liver-brain axis
in AD. In addition, we have highlighted two classes of drugs for possible repurposing (from MS and fatty liver
disease) We have informed three other consortia within AMP-AD about their putative targets, supporting them
with links to biochemical pathways and bringing seemingly diverse omics findings to common biochemical
pathways. During AMP-AD Phase II, we propose to expand metabolomic analyses to accelerate AMP-AD
progress towards novel drug discovery. By working with AMP-AD partners, we will systematically address
contributions of peripheral metabolism to brain health and disease and will provide biochemical readouts as an
intermediate phenotype for rich omics data generated in the consortium. By profiling and analyzing samples
from large community studies pre-symptomatically and by building an Atlas connecting genotypes and
metabolomic signatures of AD we hope to provide biochemical insights about mechanisms and sub-classes of
disease. In summary, the ADMC will provide an enabling metabolic interconnecting framework to accelerated
AD therapeu...

## Key facts

- **NIH application ID:** 10251372
- **Project number:** 5U01AG061359-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Rima F Kaddurah-Daouk
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,619,858
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10251372

## Citation

> US National Institutes of Health, RePORTER application 10251372, Metabolomic Signatures for Disease Sub-classification and Target Prioritization in AMP-AD (5U01AG061359-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10251372. Licensed CC0.

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