# Tau, amyloid, & white matter burden interact to impact brain networks in preclinical Alzheimer's disease

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $846,646

## Abstract

PROJECT SUMMARY
This project investigates the unique and joint impact of tau and amyloid pathology associated with Alzheimer's
disease and of white matter hyperintensities of presumed vascular origin on brain network function and
cognition, including memory and executive abilities. The overarching hypothesis is that tau, amyloid, and white
matter burden interact to specifically disrupt the function of brain networks in which the burden occurs, and will
lead to declines in cognitive abilities associated with the disrupted networks. The proposed work builds on
recent advances in the connectomics of functional networks within individuals using magnetic resonance
imaging and a recently-developed positron emission tomography marker for the visualization of tau burden in
humans. The first specific aim tests for differential and interactive influences of tau, amyloid and white matter
burden when these pathological markers occur within a brain network. The second specific aim tests for how
interactions between tau, amyloid, and white matter burden may lead to declines in cognition over a 3-year
period. The proposed work provides novel extensions of recent cross-sectional findings relating network
function, pathology, and cognition to critically test whether tau and amyloid burden interact with white matter
burden to impact regional network integrity and cognition during the preclinical stage of Alzheimer's disease. If
successful, these aims will provide evidence that localized preclinical tau and amyloid pathology and white
matter hyperintensities of presumed vascular origin have an interactive impact that contributes to the functional
network and cognitive declines commonly observed during aging. This work will help to differentiate processes
attributed to typical aging and development from the pathology associated with Alzheimer's disease at its
earliest stages. If successful, this work will improve our understanding of how the location of pathology impacts
specific brain networks and cognitive abilities, and will provide measures to improve early diagnosis of network
or cognitive dysfunction attributable to the location of these pathological markers in individual patients.

## Key facts

- **NIH application ID:** 9894702
- **Project number:** 5R01AG053509-05
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Julius C Hedden
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $846,646
- **Award type:** 5
- **Project period:** 2016-09-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9894702

## Citation

> US National Institutes of Health, RePORTER application 9894702, Tau, amyloid, & white matter burden interact to impact brain networks in preclinical Alzheimer's disease (5R01AG053509-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9894702. Licensed CC0.

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