# Determinants of neurodegenerative decline in the aphasic variant of Alzheimer's disease

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $886,421

## Abstract

PROJECT SUMMARY/ABSTRACT:
 Primary progressive aphasia (PPA) is a clinical dementia syndrome caused by neurodegenerative brain disease, with
language impairment as the primary feature. PPA is associated with two main classes of underlying neuropathology:
Alzheimer’s disease (AD) neuropathology and frontotemporal lobar degeneration (FTLD) neuropathology. Research
advances, knowledge and interest in dementias due to FTLD have flourished over the past few years allowing for new
dedicated resources (e.g., Advancing Research and Treatment for Frontotemporal Degeneration [ARTFL]), which
promise exciting new opportunities for advancing our understanding the disease and for developing therapeutics.
Unfortunately, individuals with PPA due to AD have been largely orphaned during this process; failing to meet pathologic
inclusion criteria for FTLD studies and failing to meet clinical criteria for AD clinical trials, which tend to focus on
individuals with the more typical amnestic phenotype. This is unfortunate because individuals with PPA due to AD
represent up to 45% of all PPA cases and these individuals are potentially viable candidates for AD-related therapeutics.
The proposed study will longitudinally and quantitatively characterize the clinical, cognitive, functional,
neuroanatomic and molecular features of individuals with PPA who have biomarker findings consistent with AD
(termed PPA-ADbio+ for this project). Aim 1a will quantitatively characterize longitudinal changes in morphometry
(using structural MRI), functional connectivity (using resting state MRI), tau accumulation (with [18F]-AV-1451 Tau-
PET) and clinical profiles (using detailed neuropsychological testing) of 50 PPA-ADbio+ participants at 3 consecutive
annual visits. Aim 1b will characterize the temporal relationship among the variables measured in Aim 1a. This project
represents one of the first prospective multidimensional studies of longitudinal course using the relatively new tau
biomarker [18F]-AV-1451 in PPA-ADbio+ individuals. In addition to their theoretical interest, the results from this study are
relevant for defining objective biomarkers of disease type and progression, which will inform therapeutic treatment
strategies for this relatively underserved dementia population.

## Key facts

- **NIH application ID:** 10116238
- **Project number:** 5R01AG056258-09
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** EMILY J ROGALSKI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $886,421
- **Award type:** 5
- **Project period:** 2012-03-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116238

## Citation

> US National Institutes of Health, RePORTER application 10116238, Determinants of neurodegenerative decline in the aphasic variant of Alzheimer's disease (5R01AG056258-09). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10116238. Licensed CC0.

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