# Investigating the effect of the MS4A locus on Alzheimer's disease

> **NIH NIH F31** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $43,920

## Abstract

Project Summary
Alzheimer's disease (AD) is a growing public health issue, affecting 5.4 million people within the United States
and an estimated 40 million people worldwide. It is the leading cause of dementia and manifests as
progressive decline in memory, cognitive, and motor function. Most therapies in development for AD are based
on the amyloid cascade hypothesis, which assumes that amyloid plaques are causal in AD. However, these
approaches have so far failed to yield effective treatments to prevent or cure AD. Our lab uses genetics to
identify additional genes and pathways that may be contributing to AD in order to identify new drug targets. In
this proposal, we focus on the MS4A gene family, which has been associated with AD through genome-wide
association studies (GWAS). MS4A genes are specifically expressed within myeloid cells, including microglia,
suggesting that these cell types mediate the connection between these genes and AD. Our work has shown
that alleles associated with reduced risk for AD are associated with lower levels of expression for MS4A genes.
This proposal combines genetic and cell-based approaches to characterize this gene family and investigate its
impact on myeloid cells and microglia. We hypothesize that variants within the MS4A GWAS locus affect
expression of MS4A genes, that these changes in expression disrupt myeloid cell pathways linked to
cholesterol metabolism and phagocytic clearance, and that decreased MS4A gene expression in human stem
cell-derived microglia will disrupt microglial function. Our ultimate goal is to use this functional genomics
approach to characterize this gene family as a potential drug target for new AD therapies.

## Key facts

- **NIH application ID:** 9984217
- **Project number:** 5F31AG059337-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Anastasia Efthymiou
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $43,920
- **Award type:** 5
- **Project period:** 2018-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984217

## Citation

> US National Institutes of Health, RePORTER application 9984217, Investigating the effect of the MS4A locus on Alzheimer's disease (5F31AG059337-03). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/9984217. Licensed CC0.

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