# Dissecting neuron-microglia-astrocyte interaction in AD pathogenesis

> **NIH NIH RF1** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2020 · $4,950,325

## Abstract

PROJECT SUMMARY/ABSTRACT
The long-term goal of this project is to understand the age-related, neuron-microglia-astrocyte-specific proteome
dynamics and interaction in the brain and their deregulation in the pathogenesis of Alzheimer’s disease (AD).
Our ongoing large-scale profiling of transcriptome and proteome in bulk AD brain tissue have revealed that the
transcriptome is often not an accurate indicator of protein abundance, due to posttranscriptional events, such as
protein turnover. Genetic studies have revealed over 20 AD-related genes, many of which are associated with
specific cell types. We hypothesize that dysfunction of neuron-microglia-astrocyte interaction contributes to AD
pathogenesis, and propose to use the latest cutting edge technologies to profile cell type specific proteome, in
situ transcriptome, and proteome turnover in the three cell populations from multiple common AD-related mouse
models, to decipher molecular signaling networks in disease development, and to validate targets in human AD
cases, mouse models, and human organoid models. Three specific aims are: (i) to disentangle dynamic neuron-
microglia-astrocyte-specific proteome and interaction in AD mice by BONCAT-mediated single cell type
proteomics and spatial transcriptomics, (ii) to measure cell type-specific proteome-wide protein turnover in AD
by BONCAT pulse-chase analysis, and (iii) to study deregulation of proteome dynamics in human AD cases,
mouse models and brain organoids. Successful outcome of this project will identify novel, cell type specific
molecular components and pathways regulating cell-cell interactions during AD pathogenesis, which may
provide new therapeutic strategies for effective treatment of this devastating disorder.

## Key facts

- **NIH application ID:** 10046195
- **Project number:** 1RF1AG068581-01
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** JUNMIN PENG
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $4,950,325
- **Award type:** 1
- **Project period:** 2020-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046195

## Citation

> US National Institutes of Health, RePORTER application 10046195, Dissecting neuron-microglia-astrocyte interaction in AD pathogenesis (1RF1AG068581-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10046195. Licensed CC0.

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