# Project 7: Primary Progressive Aphasia

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $145,846

## Abstract

ABSTRACT
Primary progressive aphasia (PPA) is one of the clinical presentations of the frontotemporal dementia-
spectrum disorders. It occurs when neurodegeneration selectively targets the language networks of the brain.
Discoveries from previous cycles of this PPG were fundamental in characterizing PPA and its main clinic-
anatomical presentations: the nonfluent/agrammatic (nfvPPA), semantic (svPPA) and logopenic (lvPPA)
variants. These three syndromes are associated with specific patterns of language and anatomical damage,
and are each thought to have different probable underlying molecular causes. Despite these significant
advances in PPA characterization, many questions regarding clinical heterogeneity, prognosis and biological
basis remain unanswered. In this project, we will take advantage of the wealth of multidisciplinary expertise
and data available through this PPG to investigate differential diagnosis, clinical and neuroimaging progression
and in-vivo pathological prediction in PPA. We propose a five-year cross-sectional and longitudinal study of the
cognitive, anatomical and biological features of more than 100 newly recruited individuals with PPA. We will
use the most modern techniques, from computerized, tablet-based cognitive tests to molecular neuroimaging
and gene expression, to develop principles and diagnostic concepts that can also be applied in less
specialized settings. In particular, in Aim 1 we will use validated and tablet-based tests of visuo-spatial,
executive and socio-emotional functions to study non-language features in the PPA variants. We hypothesize
that specific patterns of cognitive dysfunction will be found in each PPA variant at presentation and at 1-year
follow-up, depending on the anatomical network involved. In Aim 2, we will use the human healthy connectome
architecture to predict longitudinal neuroimaging changes in PPA. Based on the transynaptic-spread theory of
neurodegeneration, we hypothesize that regions strongly connected to syndrome-specific epicenters will show
atrophy and molecular PET changes at one-year follow-up. Finally, in Aim 3, we will combine clinical,
neuroimaging, genetic and pathological data in the largest and most comprehensive PPA dataset ever
examined, in a multivariate analyze that will determine whether molecular diagnosis can be predicted in-vivo.
This project will provide crucial data for the diagnosis of neurodegenerative diseases in their early stages,
when treatment can be most effective.

## Key facts

- **NIH application ID:** 9949609
- **Project number:** 5P01AG019724-19
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** MARIA LUISA GORNO TEMPINI
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $145,846
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9949609

## Citation

> US National Institutes of Health, RePORTER application 9949609, Project 7: Primary Progressive Aphasia (5P01AG019724-19). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9949609. Licensed CC0.

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