# Innate immune dysregulation in Alzheimer's disease modeled in Drosophila

> **NIH NIH R21** · BROWN UNIVERSITY · 2020 · $226,596

## Abstract

Summary
We propose that tau modulates innate immunity and AMPs in the brain, and thereby contributes to progression of
Alzheimer’s disease. We will test this idea with Drosophila, where tau dysregulation is produced by a human
neurodegeneration-associated mutation introduced into the fly’s endogenous tau, as well as by classic tau over-
expression. In both models, tau dysregulation causes age-dependent decline in locomotion and olfaction. Tau over-
expression produces neuropathology, and we will assess these traits in our new tau-mutant model. Central to our
proposal, we find that expression of genes for innate immunity are dramatically altered in the tau-mutant model.
Elevated innate immune expression is a common feature of aging Drosophila, where data demonstrates it contributes
to mortality and, potentially, to neurodegeneration. With our observations, we propose that tau dysregulation drives
innate immune AMPs to a pathogenic level in the brain of aging Drosophila, causing age-dependent
neurodegeneration. In this view, a similar process may well occur in humans that drives the accumulation of Ab. If so,
AD might be managed in terms of what drives, regulates and dysregulates innate immunity in the aging brain

## Key facts

- **NIH application ID:** 9971086
- **Project number:** 1R21AG067323-01
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** MARC TATAR
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $226,596
- **Award type:** 1
- **Project period:** 2020-09-30 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971086

## Citation

> US National Institutes of Health, RePORTER application 9971086, Innate immune dysregulation in Alzheimer's disease modeled in Drosophila (1R21AG067323-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9971086. Licensed CC0.

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