# Clinical, Neuroanatomic, and Pathologic Signatures of FTLD-tau in Dementia Phenotypes - Diversity Supplement

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $21,350

## Abstract

Frontotemporal
variety
lobar degeneration (FTLD) i s a neurodegenerative disease found at autopsy that underlies a
of clinical dementia syndromes, and is the second most common cause of dementia under age 65 [1].
Patients with FTLD-related dementias are underserved in part because the complex relationship between
dementias and underlying pathology is not well understood. Much of the complexity lies in the fact that the same
pathology
caused
dementia
can cause different dementia syndromes and, conversely, that a single dementia syndrome can be
by multiple pathologies. T he goal of this proposal is to disentangle the complex relationship between
syndromes, anatomic atrophy, cell death, and a specific form of FTLD, known as FTLD-tau.In doing
so, this work will help identify the putative substrates of neurodegeneration in FTLD-tau.
 This study focuses on a robust cohort of postmortem human specimens that show the most common forms
of FTLD-tau: Pick's disease, corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP). These
tauopathies can underlie primary
progressive
syndrome
cellular features of a single tauopathy (Pick's disease) in
syndromes:
dementia
model
will
cases
stereological
clinical
central
show
high PPA and bvFTD,
specifically, offer exciting opportunities for exploring the organization and pathologic targets of anatomic
networks in neurodegenerative diseases. Outcomes of this multidisciplinary study will clarify
progressive aphasia (PPA), a clinical dementia syndrome characterized by
language impairment, and behaviora l variant frontotemporal dementia (bvFTD), a clinical dementia
characterized by progressive changes in comportment. Aim 1 will determine the 
 cases diagnosed antemortem with different dementia
the semantic and agrammatic variants of PPA (PPA-S and PPA-G, respectively) and bvFTD. These
syndromes are each associated with distinct patterns of atrophy and clinical profiles, providing an ideal
to explore the selective vulnerabilities of anatomic regions responsible for cognition or behavior. Aim 2
 study the converse relationship by investigating multiple pathologies Pick's disease, CBD, and PSP) in
diagnosed antemortem with a single dementia syndrome (PPA-G or bvFTD). Histological and unbiased
methods will be used to determine relationships between FTLD-tau pathology, not only to detailed
profiles and quantitative MRI atrophy patterns, but also to neuronal, glial, and synaptic abnormalities. A
 hypothesis of t his work is that regional distributions of FTLD-tau — and related cellular features — will
 concordance with anatomic patterns of atrophy and distinct clinical profiles.
This is one of the first works of its kind that aims to establish clinical, anatomic, and pathologic concordance of
specificity between clinical dementia syndromes and the tauopathies that cause them.
specific targets and
(
 the pathologic
underpinningsof clinical heterogeneity in dementias,sharpen our understanding of the principles of s...

## Key facts

- **NIH application ID:** 10357251
- **Project number:** 3R01AG062566-02S1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Tamar D Gefen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $21,350
- **Award type:** 3
- **Project period:** 2020-01-15 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10357251

## Citation

> US National Institutes of Health, RePORTER application 10357251, Clinical, Neuroanatomic, and Pathologic Signatures of FTLD-tau in Dementia Phenotypes - Diversity Supplement (3R01AG062566-02S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10357251. Licensed CC0.

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