# Functional analysis of glia in tauopathy

> **NIH NIH RF1** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $2,531,613

## Abstract

Alzheimer's disease is the most common neurodegenerative disorder and is characterized clinically by
cognitive dysfunction. Classic neuropathological features of the disease include the formation of
extracellular amyloid plaques, intraneuronal deposition of abnormally phosphorylated and aggregated tau
protein into neurofibrillary tangles, and gliosis. Glial pathology has generally been considered a secondary,
or reactive, change. However, recent advances in understanding normal and pathological glial biology have
instead suggested that glia may play an active role in neurological disorders, including Alzheimer’s disease.
Here we take a genetic approach to define proteins and pathways mediating the influence of glia on
Alzheimer’s-associated neurodegeneration. Taking advantage of the advanced molecular and genetic tools,
short lifespan, and conserved glial biology in Drosophila we will identify glial proteins and pathways that can
influence tau neurotoxicity in aging adult brains. In proof of principle studies, we have validated a novel
system for studying non-cell autonomous neurodegeneration in tauopathy and show that our assay system
works in the context of unbiased screening. In addition, based on the observation that many genes
implicated in Alzheimer’s disease through genome wide genetic association studies (GWAS) are expressed
predominantly or substantially in glial cells, we will test the effect of upregulating and downregulating these
GWAS-derived gene candidates in fly glia on tau-induced neurotoxicity. To additionally connect our genetic
model experiments with the authentic human disease, we will use state-of-the-art informatics tools to
integrate functional genetic data with Alzheimer’s disease transcriptomics and proteomics. Since our
systems analysis will be performed on a glial subtype-specific basis our studies can not only outline glial
networks modulating the toxicity of tau to neurons, but also provide functional insight into newly defined glial
subtypes. Our studies will develop fundamental insights into glia cell biology in health and disease and will
expand the array of cellular and molecular targets relevant for therapy development in Alzheimer’s disease
and related neurodegenerative disorders.

## Key facts

- **NIH application ID:** 10523584
- **Project number:** 1RF1AG076214-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** MEL B FEANY
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,531,613
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10523584

## Citation

> US National Institutes of Health, RePORTER application 10523584, Functional analysis of glia in tauopathy (1RF1AG076214-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10523584. Licensed CC0.

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