# Seeds and Strains Derived from Tau Monomer

> **NIH NIH RF1** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $3,179,511

## Abstract

PROJECT SUMMARY/ABSTRACT
Alzheimer disease (AD) and related tauopathies are major diagnostic, therapeutic, and clinical
challenges. Our previous work suggest that different tauopathies are based on unique tau aggregate
conformations, or “strains,” and that strain identity predicts specific disease progression patterns in
animal models. We hypothesize that distinct, self-propagating tau strains can move between cells of
the brain to propagate pathology in humans. Recent publications from our group indicate that tau
monomer in fact encodes strains. However this has not been rigorously tested across tauopathies.
We will test this idea first by determining whether tau monomer encodes the same sets of strains
encoded by larger assemblies in human brain (Aim 1). Next we will use multiplex biosensors to
classify monomer from human tauopathies, and determine whether monomer can classify individuals
in correlation with neuropathology with the same fidelity as larger assemblies. We will also test the
fidelity of strain propagation in human neurons vs. HEK293 cells in comparison those strains isolated
directly from human brain (Aim 2). Finally, we use structural biology approaches to determine the
conformations of seed-competent monomer. In particular, we will determine whether local structures
in tau predict its subsequent assembly into fibrils. This will be based on crosslinking mass
spectrometry, molecular modeling, cryoEM, and microcrystallography. We predict that tau monomer
will encode strain composition across tauopathies. If we are successful, we anticipate ultimately that it
will be possible to classify tauopathies based on the conformation with tau monomer. This could have
important implications for accurate diagnosis and personalized therapy.

## Key facts

- **NIH application ID:** 10058234
- **Project number:** 1RF1AG065407-01A1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** MARC I DIAMOND
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $3,179,511
- **Award type:** 1
- **Project period:** 2020-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10058234

## Citation

> US National Institutes of Health, RePORTER application 10058234, Seeds and Strains Derived from Tau Monomer (1RF1AG065407-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10058234. Licensed CC0.

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