# Structure and Genesis of tau Aggregates

> **NIH NIH RF1** · OHIO STATE UNIVERSITY · 2022 · $1,821,723

## Abstract

PROJECT SUMMARY
Tau aggregation is a shared pathology of Alzheimer's disease and related dementias known as tauopathies.
Despite commonalities in aggregation mechanism, each disorder develops unique filamentous morphologies
that reflect differential vulnerability of their constituent cell populations. In addition to providing clues about the
cellular conditions associated with tauopathic neurodegeneration, the appearance of unique polymorphs in each
tauopathy implicates prion-like mechanisms of templating and spread that may influence the course and severity
of disease. As a result, aggregate polymorphism is a potential target for therapeutic intervention as well as for
differential diagnosis of tauopathies through development of whole-brain imaging methods. This proposal seeks
to advance these goals by clarifying mechanisms underlying aggregate nucleation, propagation and interaction
with small-molecule probes using biochemical and structural biological approaches. Specifically it aims to (1)
determine the effects of aggregation inducers including tau phosphorylation on polymorph formation, (2) clarify
mechanisms through which nucleation sequence motifs common to all tau isoforms trigger aggregation, (3)
rigorously test whether tau polymorphism can propagate through prion-like seeding mechanisms, and (4) identify
molecular interactions that mediate the binding affinity and selectivity of tau-aggregate directed ligands.
Accomplishing these goals will clarify the molecular basis of tauopathy pathogenesis and catalyze efforts toward
creating novel diagnostic strategies tailored toward individual tau aggregate polymorphs.

## Key facts

- **NIH application ID:** 10522274
- **Project number:** 2RF1AG054018-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Jeff Kuret
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,821,723
- **Award type:** 2
- **Project period:** 2017-06-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10522274

## Citation

> US National Institutes of Health, RePORTER application 10522274, Structure and Genesis of tau Aggregates (2RF1AG054018-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10522274. Licensed CC0.

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