# Essential roles of DAP12 in tau metabolism and inflammation in Alzheimer's disease

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $423,750

## Abstract

PROJECT SUMMARY
Alzheimer’s disease is the most common cause of dementia in the elderly. Recent genetic data strongly suggest
that microglia-mediated innate immune activities may directly contribute to the AD mechanisms at early onset
and/or developmental stage of this disease. Understanding the molecular mechanisms underpinning how
microglia are functionally involved in the pathogenesis of AD is beneficial for the development of new therapeutic
strategies for AD. Our long-term objective is to dissect the function of adaptor protein DAP12 in mediating
complex signals and executing their functions in microglia involved in AD pathogenesis. Our preliminary data
revealed a global effect of DAP12 deficiency in the brain transcriptome of tau P301S mouse, which reverses the
transcriptomic changes featured in the brains of multiple AD transgenic mouse models. We further found that
DAP12 deficiency increased brain tau pathology in tau P301S mice and reduced tau degradation by cultured
primary microglia. Yet, DAP12 deficiency significantly decreased brain microgliosis in tau P301S mice.
Therefore, we hypothesize that DAP12 plays differential roles in tau metabolism and microglia-mediated
inflammation during the pathogenesis of AD. We plan to fully characterize the role of DAP12 in these two AD-
relevant cellular events mediated by microglia and tau seeding/spreading. Finally we will further determine
signaling pathways altered by DAP12 deficiency on cell type specific manner in tauopathy mice.

## Key facts

- **NIH application ID:** 10829818
- **Project number:** 5R01AG064239-05
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** WENJIE LUO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $423,750
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10829818

## Citation

> US National Institutes of Health, RePORTER application 10829818, Essential roles of DAP12 in tau metabolism and inflammation in Alzheimer's disease (5R01AG064239-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10829818. Licensed CC0.

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