# Understanding Neural Bases for Neuropsychiatric Impairments in Alzheimer's Disease Models

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2024 · $716,919

## Abstract

Project Summary
Neuropsychiatric symptoms (NPS) represent a significant but frequently overlooked facet of
Alzheimer’s disease (AD). These symptoms, which encompass non-cognitive disturbances like
apathy, depression, anxiety, agitation, and aggressiveness, are prevalent in patients with AD and
related dementias and can potentially affect the trajectory of AD progression. While AD-NPS
impose major challenges on the well-being of patients and burdens on caregivers, our
understanding of their origins, interconnections and neural mechanisms in relation to
pathophysiology remains limited. This proposed research seeks to understand the neural
foundations of NPS-related behavioral abnormalities in mouse AD models. As a starting point, we
will focus on behaviors related to apathy, and test our central hypothesis that pathological and
molecular/cellular changes in the anterior cingulate cortex (ACC) are accompanied with altered
excitation/inhibition (E/I) balance which leads to behavioral impairments, while rebalancing the E/I
may ameliorate apathy-like deficits in two mouse AD models. By combining a suite of cutting-edge
approaches, we will integrate multimodality data from behavior assessments to spatial
transcriptomics, anatomy, pathology, and neural function of the brain. In Specific Aim 1, we will
explore cortical pathological and molecular/cellular/transcriptional changes associated with the
progression of NPS-like behavioral impairments. In Specific Aim 2, we will determine how cortical
neuronal functional changes contribute to apathy-like deficits in AD. The proposed study aims to
generate new mechanistic understandings of neuropsychiatric impairments in AD, which may help
to develop novel strategies for patient care and therapeutic approaches to mitigate adverse impacts
of NPS in AD management.

## Key facts

- **NIH application ID:** 10991271
- **Project number:** 1R01AG089756-01
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Huizhong Whit Tao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $716,919
- **Award type:** 1
- **Project period:** 2024-09-30 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10991271

## Citation

> US National Institutes of Health, RePORTER application 10991271, Understanding Neural Bases for Neuropsychiatric Impairments in Alzheimer's Disease Models (1R01AG089756-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10991271. Licensed CC0.

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