# Genetics-informed dissection of human brain cell-cell communication in Alzheimer's disease progression

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2024 · $820,536

## Abstract

Abstract
AD is an age-related neurodegenerative disease and the leading cause of dementia in the United
States. It is characterized by a progressive decline of memory and cognitive impairment,
ultimately leading to dementia. Currently, more than 5.7 million Americans are affected by AD,
and this number is projected to be 16 million by 2050. Although a tremendous effort has been
devoted to AD research, there are no effective disease modifying drugs available for AD, largely
due to the lack of understanding of the complex etiology of AD. Although the ultimate damage in
AD brain is neuronal loss, multiple cell types in brain are involved in AD development and
progression. Glia cells, e.g. microglia and astrocytes, are crucial for brain healthy brain. Other cell
types, e.g. vasculature cells including pericytes and endothelia cells, the major components of
brain-blood barrier, and oligodendrocytes, which is responsible for myelination of axons, are all
implicated in AD. How these key cell types interact during AD development, and in particular how
glia cells, e.g. microglia and astrocytes, interact with neurons to lead to neuronal death, are poorly
understood. In this application, we propose to develop novel analytic approaches to dissect cell-
cell communication (CCC) among microglia, astrocytes and neurons, and how the
communications are dysregulated during AD progression, and validate the candidate CCC in
human iPSC-derived cortical organoids. Specifically, we will develop novel network-based models
and statistical methods to identify CCC linked to AD pathogenesis (Aim 1), apply the developed
methods to analyze public single cell -omics data to identify CCC linked to AD pathology and
cognitive function (Aim 2), and validate the candidate CCC in human iPSC-derived cortical
organoids to decipher the multi-cellular communications underlying AD development (Aim 3).

## Key facts

- **NIH application ID:** 10991941
- **Project number:** 1R01AG089717-01
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** BINGSHAN LI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $820,536
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10991941

## Citation

> US National Institutes of Health, RePORTER application 10991941, Genetics-informed dissection of human brain cell-cell communication in Alzheimer's disease progression (1R01AG089717-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10991941. Licensed CC0.

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