# Tau-induced connectome imaging markers of Alzheimer's disease

> **NIH NIH RF1** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $2,130,568

## Abstract

Abstract
Hyperphosphorylated tau tangle is a defining hallmark of the Alzheimer’s disease (AD). Neuropathological and
recent tau PET imaging studies suggest that tau deposition has a much stronger correlation with clinical
symptoms than do amyloid plaques. The Braak staging suggests the neuron-to-neuron propagation of tau
pathology through axonal pathways, which has been supported with increasing evidence from animal and post-
mortem human studies. Limited research, however, has been conducted for the in vivo examination of
connectivity changes of fiber pathways involved in tau pathology propagation. There is thus a clear knowledge
gap regarding WHEN (specific tau pathology stage) and WHERE (specific fiber pathways) tau-induced
connectivity changes occur during the disease course of AD. Building upon our extensive track record in
connectome modeling and brain surface mapping, in this project we will develop novel computational tools for
the systematic examination of different types of fiber pathways involved in the propagation of tau pathology: the
short association fibers in the superficial white matter (SWM), the long association fibers within each hemisphere,
and the commissural fibers connecting the two hemispheres. Our project will leverage existing tau PET and
connectome imaging datasets that include: ADNI3 for late onset AD (LOAD) and the Estudio de la Enfermaded
de Alzheimer en Jalisciences (EEAJ) study for autosomal dominant AD (ADAD). This provides us the unique
opportunity to study ADAD and LOAD as being on an AD continuum and obtain a more complete characterization
of the fiber pathways affected by the tau pathology from the early prodromal stage to the ultimate onset of AD.
In addition, we will use an independent dataset (n=2000) from the Health & Aging Brain among Latino Elders
(HABLE) study to validate the generalizability of our computational tools and connectome imaging makers to the
Mexican American population. There are three specific aims in this project: 1. To develop novel computational
tools for measuring superficial and deep white matter connectivity associated with tau propagation. 2. To map
tau-induced connectivity changes of fiber pathways in AD. 3. To develop connectome-based prediction of tau-
related cognitive changes in AD. Our project will for the first time provide the comprehensive and in vivo
characterization of the fiber pathways affected by tau pathology in AD. This will help elucidate the role of different
fiber pathways in the propagation of tau pathology at different disease stages, in particular the U-fibers in the
SWM and the commissural fibers responsible for inter-hemispheric communications. The results from our study
will provide more targeted connectome imaging makers for the early prediction of AD, especially in studies
without tau PET imaging. All computational tools developed in this project will be freely distributed to the research
community to enable other AD imaging researchers for more robust ...

## Key facts

- **NIH application ID:** 10062748
- **Project number:** 1RF1AG064584-01A1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Yonggang Shi
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,130,568
- **Award type:** 1
- **Project period:** 2020-09-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10062748

## Citation

> US National Institutes of Health, RePORTER application 10062748, Tau-induced connectome imaging markers of Alzheimer's disease (1RF1AG064584-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10062748. Licensed CC0.

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