# Structural analysis of tau associated with parenchymal and vascular prion protein amyloidosis

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2024 · $750,707

## Abstract

Project Summary/Abstract
 Recently, significant progress in understanding Tau aggregation and how Tau aggregates lead
to neurodegeneration has been made by the description of the atomic structures of Tau filaments
isolated from brain. The atomic models of Tau in Alzheimer disease (AD), Pick disease,
Corticobasal degeneration, and Chronic Traumatic Encephalopathy were determined by cryo-
electron microscopy (cryo-EM) through an ongoing collaborative effort between our laboratory at
Indiana University and the MRC Laboratory of Molecular Biology. Additional Tau structures are
also currently being identified in a collaborative effort between Indiana University and Purdue
University. The studies proposed in this MPI application are a logical continuation of this
groundbreaking work. The main goals of this project are to elucidate the structural basis and
pathological mechanisms implicated in Gerstmann-Sträussler-Sheinker (GSS, F198S) disease
and Prion protein cerebral amyloid angiopathy (PrP-CAA, Q160X), in which Tau deposits are
composed by 3R+4R Tau, as in AD. We will determine the atomic structure of Tau through cryo-
EM, the role of post-translational modifications of Tau filaments in relation to structure and perform
in vitro and in vivo analysis of Tau seeding and propagation. The investigation of what drives the
specificity of Tau conformers in Tau pathology is an essential step toward the design of novel
diagnostic and therapeutic molecules.

## Key facts

- **NIH application ID:** 10891790
- **Project number:** 4R01AG071177-02
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** BERNARDINO Francesco GHETTI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $750,707
- **Award type:** 4N
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10891790

## Citation

> US National Institutes of Health, RePORTER application 10891790, Structural analysis of tau associated with parenchymal and vascular prion protein amyloidosis (4R01AG071177-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10891790. Licensed CC0.

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