# Mapping protein interactome of TREM2 and its variants to probe the etiology of Alzheimer's Disease

> **NIH NIH R21** · OHIO STATE UNIVERSITY · 2022 · $196,875

## Abstract

Project summary
 Triggering receptor expressed on myeloid cells 2 (TREM2) recently emerged as a major
immune signaling hub that is essential to sustain the microglial response to AD pathology, and
enable microglial transition to a disease-associated microglia (DAM) status. Rare variants R47H
and R62H in TREM2 significantly increase risks for late-onset Alzheimer’s disease (AD),
indicating altered TREM2 signaling is sufficient to drive AD pathology.
 Despite the exciting genetic studies linking TREM2 variants to AD etiology, the molecular
mechanisms underlying this genotype-phenotype relationship are only partially explained.
Protein-protein interactions (PPIs) are central to the proper functioning of cellular signaling and
regulatory processes, and disruptions of the normal patterns of PPIs are often observed and
implicated in human genetic diseases. As such, mapping proteins that interact with TREM2 on a
system-wide level is fundamental for understanding molecular machinery of TREM2 pathway
and dissecting specific microglial signaling that is altered in AD-associated TREM2 variants. In
this application, We propose to map TREM2 protein interactome in microglia use TurboID-
based proximity labeling approach (Aim 1), and to profile the change of TREM2 interactome
caused by AD-associated variations R47H and R62H (Aim 2). Upon completion, our study will
identify novel regulators of TREM2 signaling, and bring insights into the causal mechanisms of
TREM2 variants in AD. Knowledge generated from this project will also help design novel
therapeutic strategies targeting TREM2 for the treatment of AD.

## Key facts

- **NIH application ID:** 10370642
- **Project number:** 1R21AG075875-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Jie Gao
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $196,875
- **Award type:** 1
- **Project period:** 2022-06-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10370642

## Citation

> US National Institutes of Health, RePORTER application 10370642, Mapping protein interactome of TREM2 and its variants to probe the etiology of Alzheimer's Disease (1R21AG075875-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10370642. Licensed CC0.

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