# Elucidating the role of Chi3l1 in mediating astrocyte/microglia cross-talk and promoting neurodegeneration in AD

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2022 · $390,000

## Abstract

PROJECT SUMMARY
The goal of this proposal is to elucidating the role of Chi3l1 in mediating astrocyte/microglia cross-talk and
promoting neurodegeneration in AD. Chi3l1 is a glycoprotein widely described as a biomarker to diagnose,
predict and monitor Alzheimer's disease (AD). Chi3l1 has been detected in astrocytes in postmortem human
frontal cortexes from AD patients. The numbers of Chi3l1-postive astrocytes are associated with tau pathology
and cognitive impairment. Soluble Chi3l1 are also detected in cerebrospinal fluid (CSF), and its levels correlate
with those of total tau and p-tau. Moreover, the CSF levels of Chi3l1 are higher in mild cognitively impaired (MCI)
and AD patients, compared to cognitively normal individuals.
Despite the strong clinical correlation between Chi3l1 and AD, there are only three published mechanistic studies
investigating the role of Chi3l1 in -amyloid pathology using mouse models. Furthermore, the functional
involvement of Chi3l1 in AD tauopathology is completely unknown. Our preliminary data showed that Chi3l1
transcript levels are significantly elevated in the brains of two tauopathy mouse models. We previously
demonstrated that the secreted Chi3l1 engages with CD44 receptor on macrophage to mediate inflammatory
injury of the liver. These findings led to our hypothesis that Chi3l1 plays a critical role in AD tauopathy
through mediating astrocyte/microglia cross-talk and promoting neuroinflammation. We propose three
Specific Aims to (1) Map Chi3l1 expression in the brain with progressive tauopathy, (2) Investigate the function
of Chi3l1 in neurodegeneration associated with tauopathy, and (3) Examine the effect of Chi3l1 on microglia in
promoting neuroinflammation in tauopathy.

## Key facts

- **NIH application ID:** 10498492
- **Project number:** 3R01DK122708-03S1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Wei Cao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $390,000
- **Award type:** 3
- **Project period:** 2022-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10498492

## Citation

> US National Institutes of Health, RePORTER application 10498492, Elucidating the role of Chi3l1 in mediating astrocyte/microglia cross-talk and promoting neurodegeneration in AD (3R01DK122708-03S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10498492. Licensed CC0.

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