# Investigating the role of microRNAs in microglia in a mouse model of Alzheimer’s Disease

> **NIH NIH F30** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $42,080

## Abstract

Project Summary/Abstract
Alzheimer's Disease is the leading cause of dementia and is pathologically characterized by extracellular
amyloid plaques, tau protein aggregates in the brain, and microgliosis. Microglia are the resident innate
immune cells of the central nervous system (CNS) and recent genome-wide association studies have linked
mutations in microglial genes to increased risk of developing late-onset Alzheimer's Disease. One of the main
functions of microglia is phagocytic clearance of debris including extracellular tau, and microglia uptake of tau
has been implicated in tau pathology. Therefore, a deeper understanding of microglial phagocytosis and its
regulation in disease is necessary to understand the mechanism of tau aggregation in Alzheimer's Disease
and to identify new therapeutic targets. MicroRNAs (miRNAs) are small, non-coding RNAs that inhibit
translation of their target mRNAs, and their expression has been shown to be dysregulated in AD patients with
some of these miRNAs targeting innate immune pathways. It is, however, not well understood what miRNAs in
microglia modulate cell function and whether microglial miRNAs can modulate tau pathology.
Our preliminary studies show that loss of mature miRNAs in microglia exacerbates tau pathology in male
tauopathy mice. We hypothesize that loss of miRNAs in microglia decreases the cell's ability to degrade tau,
leading to increases in extracellular tau, and exacerbating aggregation of tau in neurons. In this proposal, we
outline two aims to test this hypothesis. In Aim 1, we will test the hypothesis that loss of mature miRNAs in
microglia decreases the cell's capacity to degrade tau in vitro and in vivo. In Aim 2, we will test the hypothesis
that the most highly-expressed miRNA in microglia, miR-16-5p, is necessary and sufficient for degradation of
tau by microgila and can modulate tau pathology in vivo. These experiments will shed insight onto miRNA-
regulation of tau phagocytosis and degradation and its contribution to tau aggregation. Completion of these
aims will yield insights into new pathways regulating the innate immune system in tauopathies and uncover
potential targets for miRNA-based therapeutics in Alzheimer's Disease.

## Key facts

- **NIH application ID:** 9977773
- **Project number:** 5F30AG062043-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Lay Kodama
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $42,080
- **Award type:** 5
- **Project period:** 2018-09-01 → 2021-08-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977773

## Citation

> US National Institutes of Health, RePORTER application 9977773, Investigating the role of microRNAs in microglia in a mouse model of Alzheimer’s Disease (5F30AG062043-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9977773. Licensed CC0.

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