# Project 2 - Imaging of Brain Connrectivity, Structure and Function

> **NIH NIH P01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2023 · $895,592

## Abstract

Project 2 – Project Summary / Abstract
 Alzheimer’s disease (AD) is the most common cause of cognitive impairment in older adults and affects
over 5.8 million people in the US alone. Individuals who carry the apolipoprotein E-ε4 (APOE4) gene are at
heightened risk for developing late onset AD. Project 2 of the proposed P01 renewal “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 and blood-brain barrier (BBB)
integrity and ultimately confer cognitive impairment in APOE4 carriers (e3/e4, e4/e4) relative to APOE3
homozygotes (e3/e3).
 Project 2 will follow 402 APOE4 carriers and 465 APOE3 homozygotes, initially enrolled as CU (75%)
and MCI (25%) at baseline, who will continue to be evaluated longitudinally for changes in brain connectivity in
relation to neurovascular and cognitive function. Participants will continue to receive the same imaging protocol
to enable longitudinal analyses, including 1) multi-shell DTI for white matter connectivity; 2) resting fMRI for
functional connectivity; 3) structural MRI for gray matter shape, volume; and 4) DCE-MRI for BBB integrity
(Project 1), as well as BBB/neurovascular unit (NVU) biofluid biomarkers (Core B). For preclinical AD staging,
we will follow the AT(N) biomarkers framework. For cognitive assessment, we will use the UDS 3.0 cognitive
tests and supplemental tests across different cognitive domains to evaluate the relationships between
neurovascular/BBB dysfunction and biomarkers, structural and functional connectivity, and cognitive function
following the AT(N) research framework. Participants will also complete amyloid and tau PET scans to examine
the effect of amyloid and tau on brain function and structure in a prespecified analysis. The role of neurovascular
integrity and brain connectivity in the pathophysiology of preclinical cognitive decline and clinical progression to
mild cognitive impairment (MCI) and AD have only begun to be elucidated. Using advanced neuroimaging
methodology, this project will apply a hypothesis-driven approach to understand how impairment in the BBB
impact brain structure and function and cognition in APOE4 carriers relative to APOE3 homozygotes.

## Key facts

- **NIH application ID:** 10621713
- **Project number:** 5P01AG052350-07
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** ARTHUR W TOGA
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $895,592
- **Award type:** 5
- **Project period:** 2016-09-30 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10621713

## Citation

> US National Institutes of Health, RePORTER application 10621713, Project 2 - Imaging of Brain Connrectivity, Structure and Function (5P01AG052350-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10621713. Licensed CC0.

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