# Identifying Alzheimer’s Disease Causal Variants and Target Genes Using iPSC-derived Microglia

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $751,779

## Abstract

Project Abstract
Treatment options for Alzheimer’s disease have been elusive, in large part because the molecular mecha-
nisms underlying AD remain unclear. Genome-wide association studies (GWAS) have uncovered genomic
loci associated with increased risk of AD; however, the exact causal variants within these loci and the genes
they affect have been difficult to determine. While many lines of evidence suggest that these variants alter
transcriptional regulatory networks in microglia, primary human microglia are hard to acquire and intrac-
table for many genome-editing, genomic, and high-throughput technologies. The overall objective of this
proposal is to determine how AD causal SNPs alter microglia regulatory networks. Using microglia derived
from human induced pluripotent stem cells, we will define transcriptional regulatory networks in resting and
activated microglia (Aim 1), identify the causal SNPs within each AD GWAS locus (Aim 2), and determine the
genes affected by AD-associated SNPs (Aim 3). Accomplishment of the goals set forth here will establish
a cell culture model of microglial response to AD stimuli, determine the causal AD variants at each GWAS
locus, and identify the genes impacted by AD-associated SNPs. These results will have a positive impact
because they will identify the key genes involved in AD pathogenicity, providing a foundation for further
studies towards the development of tools to diagnose, prognose, and treat AD.

## Key facts

- **NIH application ID:** 10136504
- **Project number:** 5R01AG066871-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Todd Jonathan Cohen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $751,779
- **Award type:** 5
- **Project period:** 2020-04-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136504

## Citation

> US National Institutes of Health, RePORTER application 10136504, Identifying Alzheimer’s Disease Causal Variants and Target Genes Using iPSC-derived Microglia (5R01AG066871-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10136504. Licensed CC0.

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