# Targeting specific MicroRNA to alleviate Alzheimer’s Disease pathobiology

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2024 · $685,448

## Abstract

Targeting microglia to alleviate Alzheimer’s Disease pathobiology
Summary
Alzheimer’s disease (AD) is the most common cause of age-related dementia leading to irreversible
neurodegeneration and cognitive decline with no cure or effective preventive measures. Autophagy is a
conserved, cell response found in all eukaryotic cells. Several studies in AD showed that autophagy activity is
compromised in neuronal cells and suggested that this leads to reduced clearance of amyloid-β (Aβ) and
neurotoxicity. Few reports examined autophagy activity in the AD brain and suggested that autophagy is
dysfunctional in neurons, however, the contribution of autophagy in microglia, the immune cell of the brain, is
unclear. Our newly generated data that was recently published show that autophagy is impaired in adult microglia
from AD mice. More importantly, we found that a specific microRNA (miRNA), that targets several autophagy
molecules, is upregulated in the brain of AD patients when compared to non-AD individuals, as well as in the
brain and microglia-derived from an AD mouse model. Increased expression of this specific miRNA in the AD
brain leads to down-regulation of autophagy effectors, which is then responsible for reduced clearance of Aβ by
microglia. In Aim 1, we will determine the mechanism underlying elevated expression of the miR. In Aim 2, we
will investigate the functional consequences of reducing this miR in the brain of AD mouse and the mechanism
by which the microRNA is upregulated in AD brain. We will determine the behavior of microglia isolated from
treated mice. These experiments will be performed using the AD mouse model 5XFAD and human samples from
AD and non-AD patients. Our proposal will characterize a novel drug target and mode of delivery for AD.

## Key facts

- **NIH application ID:** 10831452
- **Project number:** 5R01AG082113-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Amal O Amer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $685,448
- **Award type:** 5
- **Project period:** 2023-05-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10831452

## Citation

> US National Institutes of Health, RePORTER application 10831452, Targeting specific MicroRNA to alleviate Alzheimer’s Disease pathobiology (5R01AG082113-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10831452. Licensed CC0.

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