# Data Infrastructure and Molecular Atlas for Alzheimer's Disease: Connecting Exposome, Gut Microbiome, and Metabolome.

> **NIH NIH U19** · DUKE UNIVERSITY · 2022 · $2,424,945

## Abstract

ABSTRACT – Overall
Behavioral, emotional and cognitive disorders have been historically studied as diseases of the central nervous
system (CNS). However, emerging data suggests a gut-brain connection in a variety of diseases that affect the
brain. Our own data and others’ suggests a gut-brain connection in Alzheimer’s disease (AD), a progressive
neurodegenerative disorder that is the leading cause of dementia. There are currently no therapies to prevent
or slow AD progression, causing a huge socioeconomic burden and highlighting our incomplete knowledge.
Given an emerging role for gut microbiome and hypotheses implicating viral and bacterial contributions to AD
pathogenesis, defining the bidirectional biochemical communication between the brain and the gut will improve
understanding of neurodegenerative and psychiatric diseases. Indeed, it is crucial to study the brain not in
isolation, but in the context of peripheral influences including diet, lifestyle, and microbiome. In this proposal we
build on large initiatives and infrastructures co-established by our multi-disciplinary team including: The
American Gut Project, The AD Metabolomics Consortium, Alzheimer’s Disease Research Centers (ADRCs),
National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD), The National
Alzheimer’s Coordinating Center (NACC) and centers of excellence in informatics and systems biology. We
aim to define the role of gut microbiome in AD pathogenesis and biochemical axis of communication between
gut and brain. Aim 1: Examine the association between the gut microbiome and AD phenotypes. Aim 2:
Define the biochemical axis of communication between the gut microbiome and the brain and identify
metabolites that contribute to AD endophenotypes. Aim 3: Examine mechanistic links between the
activity of the gut microbiome and AD pathogenesis, and identify new approaches for AD prevention
that target the gut-brain axis. These aims will be enabled three projects supported by an Omics and
Technology Core, a Computational and Systems Biology Core, and an Administrative Core that provides data
and biorepository infrastructure. Project 1 will define changes in gut microbiome and metabolome across the
AD trajectory; Project 2 leverages three existing clinical trials of controlled diets to examine dietary effects on
gut microbiome, metabolome, cognition and brain imaging; Project 3 examines mechanism by defining gut-
brain communication and microbiome-based interventions in animal models of AD. In this U19 we will create
an unprecedented, high-quality dataset and resources specifically for the AD research community, and make
these available under open science, FAIR (findable, accessible, interoperable, reusable) data principles. With
our cross-disciplinary team of experts in clinical AD, gut microbiome research, imaging, metabolomics,
informatics, deep learning and systems biology, this effort will yield novel biomarkers for AD progression and
prognosis, and ...

## Key facts

- **NIH application ID:** 10659795
- **Project number:** 3U19AG063744-04S1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** ROB KNIGHT
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,424,945
- **Award type:** 3
- **Project period:** 2019-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10659795

## Citation

> US National Institutes of Health, RePORTER application 10659795, Data Infrastructure and Molecular Atlas for Alzheimer's Disease: Connecting Exposome, Gut Microbiome, and Metabolome. (3U19AG063744-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10659795. Licensed CC0.

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