# Development of in vitro disease-relevant strains of tau

> **NIH NIH R21** · UNIVERSITY OF TEXAS SAN ANTONIO · 2020 · $404,500

## Abstract

Summary
The aggregation of the protein tau is associated with a wide variety of neurodegenerative diseases, including
Alzheimer's disease (AD). It has proven extraordinarily difficult to develop therapeutic strategies against AD and
AD-related disorders that modify the underlying pathologies associated with them. Because it would be
impractical to screen potential drugs against aggregates purified from disease brain tissue due to the large
amounts of materials that would be required, most studies employ tau aggregates that have been induced
artificially. Recent results have shown that the tau aggregates associated with disease have specific three
dimensional structures, and that one of the most commonly used inducers to generate tau aggregates for
therapeutic screening have a structure dissimilar from those found in disease. It is therefore critical for the field
to identify conditions that can generate tau aggregates that have structural similarity to authentic aggregates
from disease. We will take the approach of combining a wide variety of biochemical inducers with a number of
different tau variants that we predict will generate a disease-relevant strain. We will compare the strains we
generate with those we purify from AD and AD related neurodegenerative disorders such as progressive
supranuclear palsy. If we are successful in identifying an artificial disease-relevant strain, we will continue our
screening efforts to identify disease-relevant tau aggregation inhibitors while simultaneously working toward
building a library of tau aggregate strains for multiple neurodegenerative tauopathies. These efforts will not only
greatly increase the probability of generating effective therapeutics, but could also provide the possibility for
creating molecular probes for the detection and diagnosis of specific tau strains in disease.

## Key facts

- **NIH application ID:** 10055553
- **Project number:** 1R21AG069112-01
- **Recipient organization:** UNIVERSITY OF TEXAS SAN ANTONIO
- **Principal Investigator:** TRUMAN C GAMBLIN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $404,500
- **Award type:** 1
- **Project period:** 2020-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10055553

## Citation

> US National Institutes of Health, RePORTER application 10055553, Development of in vitro disease-relevant strains of tau (1R21AG069112-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10055553. Licensed CC0.

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