# Clinical Core

> **NIH NIH P01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $223,450

## Abstract

Frontotemporal degeneration (FTD) is an understudied clinical neurodegenerative condition even though it is
the most common cause of dementia after Alzheimer’s disease (AD) in people <65 years old. The most
common frontotemporal lobar degeneration (FTLD) pathology associated with FTD is TDP-43 proteinopathy
known as FTLD-TDP. Although rare mutation carriers can be identified who have FTLD-TDP pathology during
life, there are no known biomarkers for the vast majority of FTD patients with sporadic disease that can reliably
distinguish patients with FTLD-TDP histopathology from those with FTLD-Tau pathology, nor from patients who
present with clinical FTD but are atypical variants of pathological AD. This has resulted in major gaps in
knowledge that severely limit our understanding of TDP-43-associated pathophysiology, significantly constrain
the development of disease-modifying treatment trials, and severely impede designing clinical end-points to
follow for prognosis and for treatment trials. It is thus necessary to collect data that help define the specific
pathologic form of FTLD during life more accurately, and relate these data to imaging, biofluid biomarker,
genetic and autopsy data studied in this PPG. Moreover, disease-modifying treatment trials require well-
characterized natural histories of phenotypes related to FTLD-TDP in order to identify clinical markers
indicating a beneficial treatment response. The Clinical Core will work with other cores and projects to improve
our understanding of the TDP-related degeneration of multilevel neural networks examined in this Program
Project Grant (PPG). To these ends, we will recruit patients with sporadic clinical FTD who have a high
likelihood of having FTLD-TDP pathology such as semantic variant Primary Progressive Aphasia (svPPA),
behavioral variant FTD (bvFTD) co-occurring with svPPA, PPA and bvFTD with co-occurring amyotrophic
lateral sclerosis (ALS). We will also recruit symptomatic carriers of mutations associated with FTLD such as
PGRN and C9orf72. We will assess these cases annually with a brief but comprehensive neuropsychological
battery, recruit cases for imaging and biofluid studies, and recruit cases for autopsy. We propose four Specific
Aims to achieve these goals.

## Key facts

- **NIH application ID:** 9937383
- **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:** $223,450
- **Award type:** 1
- **Project period:** 2020-09-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9937383

## Citation

> US National Institutes of Health, RePORTER application 9937383, Clinical Core (1P01AG066597-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9937383. Licensed CC0.

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