# Pathology-guided 7T neuroimaging biomarker in FTLD-TDP

> **NIH NIH P01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $242,341

## Abstract

TDP-43 proteinopathy is a common form of neurodegenerative dementia (i.e. frontotemporal dementia, FTD) in
patients younger than 65 (i.e. frontotemporal lobar degeneration with TDP-43 proteinopathy, FTLD-TDP) and is
a common co-pathology in Alzheimer’s disease and aging. There are currently no biomarker modalities that
can accurately identify and track TDP-43 mediated neurodegeneration in living patients, which poses a major
obstacle for clinical trials targeting TDP-43 associated mechanisms of disease. Indeed, FTLD-TDP is an
incurable condition and cannot be reliably diagnosed and differentiated from clinically similar patients with
tauopathy (FTLD-Tau) during life, making autopsy the gold-standard for diagnosis. The overarching goal of this
project is to integrate digital histology of human brain tissue with high-resolution ex vivo 7 Tesla (7T) magnetic
resonance imaging (MRI) to model TDP-43 disease in the human brain connectome. We aim to first use ex
vivo 7T MRI guided sampling of grey matter (GM) regions important for neurocognitive networks that underly
FTD clinical symptoms and contrast the distribution of TDP-43 and clinically indistinguishable FTLD-Tau to
determine microscopic GM cellular patterns of TDP-43 protienopathy. Next, we will examine TDP-43 pathology
in uniquely sampled deep white matter (WM) tracts and contrast the distribution of TDP-43 and tau pathology
in WM pathways of neurocognitive networks using graph theoretic analysis. Finally, we will examine GM
laminar features of TDP-43 pathology in 7T MRI ex vivo imaging. Successful completion of these aims will
provide critically needed autopsy-data to guide development of histopathology-validated markers of
progressive microscopic TDP-43 disease in macroscale neurocognitive networks implicated in FTD.

## Key facts

- **NIH application ID:** 9937389
- **Project number:** 1P01AG066597-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** David John Irwin
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $242,341
- **Award type:** 1
- **Project period:** 2020-09-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9937389

## Citation

> US National Institutes of Health, RePORTER application 9937389, Pathology-guided 7T neuroimaging biomarker in FTLD-TDP (1P01AG066597-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9937389. Licensed CC0.

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