# Microbiome-microglia interactions in Alzheimer’s disease pathophysiology

> **NIH NIH F31** · EMORY UNIVERSITY · 2023 · $47,694

## Abstract

Project Summary:
 Alzheimer’s disease (AD) is a growing public health threat that places an immense burden on patients,
caregivers, and the economy. Despite a century of research and over 2,000 clinical trials, AD has limited
treatment options and no cure. The failure to develop effective therapeutics likely stems from an incomplete
understanding of AD etiology—highlighting the crucial need to identify and better understand modifiable disease
risk factors. Recent evidence suggests that, in addition to brain pathology, AD patients also display alterations
in the gut microbiome that may contribute to disease. Manipulation of the gut microbiome is sufficient to improve
or exacerbate AD-like symptoms and pathology in mouse models, suggesting that the microbiome may directly
contribute to disease development and progression. The mechanism by which the microbiome impacts disease
etiology is currently unknown, however, one possibility is through modulation of inflammatory responses. The
gut microbiome has been shown to influence the development and activation states of both peripheral and brain-
resident immune cells that are critical for amyloid clearance and neuronal health. However, the contribution of
individual AD-associated microbial species to neuroinflammatory and disease outcomes is unknown, and the
mechanisms of this gut-to-brain communication have yet to be explored. The present NRSA will address this
gap, determining the consequences of, and mechanisms by which, specific AD-associated gut microbes shape
neuroinflammatory and disease outcomes. Aim 1 will establish the effects of individual AD-associated gut
microbes on microglia functional state and response to stimulation (1.1). Furthermore, it will determine whether
these gut-to-brain signals are mediated by specific peripheral immune signals triggered by discrete bacterial
molecules (1.2). Aim 2 will concurrently determine the pathophysiological impacts of specific AD-associated
bacteria on disease outcomes (2.1) and evaluate whether microglia and specific bacterial inflammogens are
necessary for these effects. This innovative, interdisciplinary approach will provide key mechanistic links
between gut dysbiosis and AD outcomes. In addition, by identifying both microbe and host-derived cellular
pathways that impact disease state, it will identify novel and specific treatment targets for AD.

## Key facts

- **NIH application ID:** 10679850
- **Project number:** 1F31AG076332-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Lisa Blackmer-Raynolds
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $47,694
- **Award type:** 1
- **Project period:** 2023-05-03 → 2025-05-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10679850

## Citation

> US National Institutes of Health, RePORTER application 10679850, Microbiome-microglia interactions in Alzheimer’s disease pathophysiology (1F31AG076332-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10679850. Licensed CC0.

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