# Evaluation and Disruption of Tau - GSK3β Vicious Cycle

> **NIH NIH F32** · J. DAVID GLADSTONE INSTITUTES · 2021 · $2,500

## Abstract

Project Summary/Abstract
Our goal is to advance our understanding and ability to treat Alzheimer's disease. Our lab discovered that tau
reduction can prevent A-induced activation of GSK3, a kinase that is activated by many AD-relevant
pathomechanisms and has been implicated in the hyperphosphorylation of tau. We will determine which of
these mechanisms activate GSK3β in a tau-dependent manner and whether the activation involves direct
interactions between tau and GSK3β. To prevent tau-dependent GSK3 activation, we propose to reduce
overall tau levels. Tau reduction can prevent cognitive decline and neurodegeneration in mouse models of AD.
We found that blocking the rho-associated protein kinase (ROCK) pathway reduces tau levels in primary cells
and in adult mouse brain. To further explore this therapeutic strategy, we will use a new ROCK inhibitor that
has high potency and good brain penetration in mouse models.

## Key facts

- **NIH application ID:** 10398663
- **Project number:** 3F32AG062039-03S1
- **Recipient organization:** J. DAVID GLADSTONE INSTITUTES
- **Principal Investigator:** Daniel Gulbranson
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,500
- **Award type:** 3
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10398663

## Citation

> US National Institutes of Health, RePORTER application 10398663, Evaluation and Disruption of Tau - GSK3β Vicious Cycle (3F32AG062039-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10398663. Licensed CC0.

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