# Primary Progressive Aphasia: Cognition, Anatomy and Progression

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $780,730

## Abstract

ABSTRACT
Primary progressive aphasia (PPA) is a clinical syndrome characterized by isolated, progressive loss of
speech and language abilities. PPA occurs when neurodegeneration selectively targets the language networks
in the brain. It is most often caused by molecular and pathological changes typical of Frontotemporal lobar
degeneration (FTLD) or Alzheimer’s disease (AD). Over the past 12 years of this project, we have studied a
cohort of 300 well-characterized PPA patients, and have obtained an unprecedented number of post-mortem
samples. We have published more than 130 papers, and have made discoveries that were essential in
characterizing the PPA clinical variants and in defining the main clinico-anatomical presentations: the
nonfluent/agrammatic (nfvPPA), semantic (svPPA) and logopenic (lvPPA) variants, each associated with a
different probability of underlying molecular causes.
Despite this significant progress, many questions regarding cognitive presentation, clinical course and
biological basis remain unanswered. In this project, we will apply novel neuroimaging and cognitive
neuroscience techniques to study clinical symptoms, in-vivo tau deposition, longitudinal progression, and
prediction of pathological and molecular changes in PPA. We propose a five-year cross-sectional and
longitudinal study of the cognitive, anatomical and biological features of more than 200 newly recruited
individuals with PPA. In particular, in Aim 1, we will study the differential contribution of white matter, gray
matter, and functional changes in the brain to the development of PPA symptoms, and use new tasks to
investigate semantic, grammatical, and orthographic functions. In Aim 2, we will apply the novel positron
emission tomography [18F]AV1451 tau ligand to study how in-vivo molecular brain changes relate to clinical
and cognitive factors in lvPPA and nfvPPA. Finally, in Aim 3, we will study PPA progression, and the validity of
the network-spread theory of neurodegeneration, by relating longitudinal neuroimaging changes in patients to
the healthy connective architecture. Furthermore, we will perform multivariate analyses on the combined
clinical, neuroimaging, genetic, and pathological data, in the largest and most comprehensive PPA dataset
ever examined to determine whether molecular diagnosis can be predicted in-vivo.
This project will provide novel evidence on the neural basis of language, and provide crucial data for the
diagnosis of neurodegenerative diseases in their early stages, when treatment can be most effective.

## Key facts

- **NIH application ID:** 9853842
- **Project number:** 5R01NS050915-16
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** MARIA LUISA GORNO TEMPINI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $780,730
- **Award type:** 5
- **Project period:** 2004-07-15 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853842

## Citation

> US National Institutes of Health, RePORTER application 9853842, Primary Progressive Aphasia: Cognition, Anatomy and Progression (5R01NS050915-16). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9853842. Licensed CC0.

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