# Tau-associated pathological changes in reward networks for the prediction of neuropsychiatric symptoms in Alzheimer’s disease

> **NIH NIH R21** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $201,340

## Abstract

Abstract
In the diagnosis of Alzheimer’s disease (AD), cognitive changes have been the core clinical symptoms, but
neuropsychiatric symptoms (NPS) such as apathy, depression, and anxiety can also be the earliest
manifestations of AD in as many as 88% of affected persons. While alterations of the reward network in apathy
and related NPS were observed in various studies, there is relatively limited research studying the underlying
biological mechanism linking AD-specific pathology to reward network degeneration and ultimately the
development of NPS in AD. With the recent invention of tau PET imaging and revolutionary advances in human
connectome imaging techniques, we have the unprecedented opportunity to study AD-specific pathological
changes in the reward network and their consequences on the development of NPS. By leveraging existing tau
PET and connectome imaging data from two large-scale projects, we will study in this project how tau pathology
affects reward network pathways and contributes to the development of NPS in AD patients. We focus on the
tau pathology because it has been consistently shown to be more strongly correlated with clinical symptoms than
amyloid-β(Aβ) plaques. Our project also builds upon strong evidence supporting the transynaptic propagation of
tau pathology across different brain regions from both animal and human studies. There are two specific aims in
this project. 1. To develop the computational tools for systematically mapping the reward network with
connectome imaging data. 2. To determine the extent to which reward-related neuropsychiatric symptoms in AD
subjects across genetic subtypes can be predicted with tau deposition and connectivity changes in the reward
network. With an improved understanding of the propagation of AD pathology within the reward network, we can
identify the affected pathways most associated with specific NPS in AD patients, elucidating their mechanisms,
facilitating our ability to predict their development, and potentially enhancing our abilities to track response to
treatment. All the computational tools developed in this project will be freely distributed to the research
community. We believe this will fill an urgent gap in current AD research and greatly benefit the research
regarding NPS in AD.

## Key facts

- **NIH application ID:** 9998826
- **Project number:** 5R21AG064776-02
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Yonggang Shi
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $201,340
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998826

## Citation

> US National Institutes of Health, RePORTER application 9998826, Tau-associated pathological changes in reward networks for the prediction of neuropsychiatric symptoms in Alzheimer’s disease (5R21AG064776-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9998826. Licensed CC0.

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