# Project-002

> **NIH NIH P01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $720,580

## Abstract

Alzheimer’s disease (AD) is the most common cause of cognitive impairment in older adults and affects
over 5 million people in the US alone. Individuals who carry the apolipoprotein E-ε4 (APOE4) gene are at
heightened risk for developing late onset AD while individuals with the presenilin 1 (PSEN1) gene mutation will
develop autosomal-dominant AD. Project 2 of the proposed P01 “Vascular Contributions to Dementia and
Genetic Risk Factors for Alzheimer’s Disease” will provide critical advances towards discovering how changes
in brain connectivity, structure and function relate to neurovascular integrity and ultimately confer cognitive
impairment in AD genetic risk groups.
Across 5 sites, Project 2 will recruit 722 participants, including 294 APOE4 carriers and 340 non-carriers,
and 44 PSEN1 mutation carriers and 44 non-carriers, followed longitudinally to evaluate changes in
brain structure and function. Participants with NCI or early MCI will receive our imaging protocol every 2 years:
1) multi-shell DTI for white matter network connectivity; 2) resting fMRI for functional network connectivity; 3)
structural MRI for gray matter shape, volume; and 4) DCE-MRI, ASL perfusion (from Project 1); in addition to
Uniform Data Sets (UDS) cognitive tests. 150 participants (50 APOE4 carriers, 100 non-carriers) will also
complete an amyloid PET scan to examine the effect of amyloid deposition on brain function and structure. We
will address aims directed at assessing differences in structural and functional connectivity, examining the
temporal association between brain connectivity changes over time, understanding how brain connectivity
predicts future cognitive decline, and evaluating how blood-brain barrier integrity impacts brain connectivity.
The relationship between structural connectivity, functional connectivity, and neurovascular integrity has not
been explored. Using advanced neuroimaging methodology, this project will apply a hypothesis-driven
approach to understand how brain structure and function change in individuals with high genetic risk for AD,
and the impact of neurovascular integrity on these changes.

## Key facts

- **NIH application ID:** 9963136
- **Project number:** 5P01AG052350-05
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** ARTHUR W TOGA
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $720,580
- **Award type:** 5
- **Project period:** — → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963136

## Citation

> US National Institutes of Health, RePORTER application 9963136, Project-002 (5P01AG052350-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9963136. Licensed CC0.

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