# Formation and Propagation of Tau Oligomeric Strains in Alzheimer's Disease

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2024 · $776,725

## Abstract

The pathological aggregation of the microtubule-associated protein tau and its subsequent
deposition in neurofibrillary tangles (NFTs) are defining histopathological features of Alzheimer’s
disease (AD) and many other neurodegenerative disorders. Although accumulated tau protein
aggregates in the brain are a consistent hallmark of AD, there is a vast array in the progression
rate of disease and diversity in symptoms. An expansive body of evidence demonstrates that AD
shares important characteristics with prion diseases in terms of protein aggregation where
conformational variants of tau and Aβ can induce templating of aggregation in cell models or in
vivo. Recent advances have spurred a series of critical questions as i) how variable tau aggregate
strains can be, ii) formation of tau strains with the ability of spreading within the brain regions and
induce aggregation of native tau, iii) the propensity of diverse tau strains to precede and
accompany other amyloid aggregation.
Our central hypothesis is that the biological properties of AD-relevant tau oligomer strains in
specific genetic background and mixed protein pathologies are encoded in the structure of these
aggregates. Thus, the interplay/competition between distinct tau oligomer strains is a critical
determinant in controlling the extent of disease progression and initiating definite toxicity
cascades in AD. The identification of the most dominant and latent strains will be crucial for the
design of personalized therapeutic strategies by enhancing accurate targeting of the toxic
species.
This proposal is based on our excellent progress and exciting preliminary data and supported by
our competent team and collaborators, will address tau oligomeric strain biology and the
unexplored role of domination in oligomer stains, thus regulating disease progression and
phenotypes in AD, one of the most relevant contemporary NIH mission areas. The novel insights
gained from this study will lead to the future designing of clinical trials and the possibility for
personalized medicine.

## Key facts

- **NIH application ID:** 10814792
- **Project number:** 5R01AG054025-08
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Rakez Kayed
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $776,725
- **Award type:** 5
- **Project period:** 2016-07-15 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10814792

## Citation

> US National Institutes of Health, RePORTER application 10814792, Formation and Propagation of Tau Oligomeric Strains in Alzheimer's Disease (5R01AG054025-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10814792. Licensed CC0.

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