# Study of Selective Cell and System Vulnerability in Alzheimer's Disease

> **NIH NIH R56** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $1,344,626

## Abstract

PROJECT SUMMARY/ABSTRACT
 Alzheimer’s disease (AD) is a leading cause of dementia among the elderly and the most prevalent age-
related neurodegenerative disease, affecting ~56 million individuals worldwide. Despite of its high heritability
(estimates ranging 60-80%) and many genetic variants (residing in tens of loci across the genome) identified
from genome-wide association studies (GWAS), our knowledge of the underlying genetic mechanisms remains
limited. Uncovering pathophysiological mechanisms underlying AD proves to be highly challenging. To
advance our mechanistic understanding of AD, we will first acquire and harmonize various in-house, protected
and public data, encompassing bulk and single cell RNA-seq data, GWAS summary statistics, array
genotyping and whole genome sequencing data, as well as myriads of functional genomic data. We will then
analyze them using a suite of computational methods and bioinformatics tools to generate cell-type-specific
mechanistic hypotheses. These hypotheses will be validated through experimental technologies. Our
validations will be carried out in iPSC-derived neural cells (particularly excitatory neurons and microglia), as
well as in iPSC-derived brain organoids involving diverse cell types including neurons, astrocytes, and
microglia. In these iPSC-derived cells and organoids models, we will leverage CRISPRi as well as knock-in
experimental technologies to perturb the most promising putatively causal regulatory DNA elements, and
evaluate the impact by measuring a cascade of molecular and cellular phenotypes including gene expression
and AD related physiological phenotypes.

## Key facts

- **NIH application ID:** 10670502
- **Project number:** 1R56AG079291-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Li Gan
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,344,626
- **Award type:** 1
- **Project period:** 2022-09-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10670502

## Citation

> US National Institutes of Health, RePORTER application 10670502, Study of Selective Cell and System Vulnerability in Alzheimer's Disease (1R56AG079291-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10670502. Licensed CC0.

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