# Tau-mediated synaptic dysfunction in age-related neurodegenerative diseases

> **NIH NIH F99** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $40,708

## Abstract

Neurofibrillary tangles (NFTs) of the microtubule-associated protein tau are a universal feature of the aging brain.
The extent of tau pathology throughout the brain correlates with both synapse loss and severity of cognitive
impairment in age-related tauopathies. The ability to maintain cognitive function with a brain accumulating NFTs
relies on the preservation and maintenance of synaptic networks. Therefore, understanding the mechanism by
which tau contributes to network and synapse vulnerability is critical for developing preventative therapeutics.
The goal of this proposal is to determine the cellular mechanism(s) by which pathologic tau drives neuronal
network dysfunction. The experiments proposed in this application will uncover these mechanisms and provide
intellectual and technical training for a successful transition into a postdoctoral position. The F99 phase (Aim 1)
will test mechanistic cell biological hypotheses to better define how abnormal tau accumulation induces synaptic
dysfunction, while providing opportunity to develop intricate experimental design and execution skills through
cutting-edge biochemistry, microscopy, and electrophysiology techniques. The K00 phase (Aim 2) will build upon
the F99 studies with computational strategies to integrate proteomics data from humans and experimental
models to identify co-existing molecular changes that are highly relevant to age-related tauopathies.

## Key facts

- **NIH application ID:** 11032725
- **Project number:** 5F99AG083305-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Audrey Weber
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $40,708
- **Award type:** 5
- **Project period:** 2023-09-07 → 2025-09-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11032725

## Citation

> US National Institutes of Health, RePORTER application 11032725, Tau-mediated synaptic dysfunction in age-related neurodegenerative diseases (5F99AG083305-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11032725. Licensed CC0.

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