# Multi-Modal MRI to Assess Alzheimer's Disease Prevention in an APOE4 Mouse Model

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2020 · $571,376

## Abstract

Project Summary
Apolipoprotein ε4 (APOE4) allele is the strongest genetic risk factor for Alzheimer’s disease (AD).
Neuroimaging studies in humans have shown that cognitively normal APOE4 carriers develop vascular,
metabolic and structural deficits decades before the aggregation of beta-amyloid (Aβ) and neurofibrillary tau
tangles. Interventions that can restore these deficits to normal would be critical to potentially prevent the
development of AD related neuropathology and cognitive impairment. The rationale of the study is to use the
state-of-the-art, in vivo MRI methods to identify a potential intervention, Rapamcyin, for AD prevention in a
mouse model that overexpresses human Aβ via 5 familial-AD mutations, and expresses human APOE4
(E4FAD). The central hypothesis is that multi-modal MRI can be used as surrogate markers to assess efficacy
of Rapamycin for restoring brain vascular, metabolic, and structural functions in mice that carry APOE4 genes.
We will also validate our MRI results by comparison with biochemical assays, and finally compare with
behavioral outcomes. The hypothesis will be tested by pursuing three specific aims: 1) Test the hypothesis that
Rapamycin restores neurovascular functions; 2) Test the hypothesis that Rapamycin protects neurometabolic
functions; and, 3) Test the hypothesis that Rapamycin preserves structural and cognitive functions. The project
is innovative because it employs cutting-edge, multi-disciplinary novel technology to focus on early
interventions that may become an effective way to prevent AD-induced dementia for APOE4 carriers. The
project is significant because with validation, these multimodal MRI methods will dramatically enhance future
research for identifying potential therapeutics using animal models in the fields related to AD and other age-
related neurodegenerative disorders. We can also translate our approach to future human studies because all
the MRI methods used in the proposal are readily able to be used in humans. Because Rapamycin is FDA-
approved, the findings from the study will also provide valuable information, and may pave a way, for future
Rapamycin clinical trials to prevent dementia for pre-symptomatic APOE4 carriers.
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## Key facts

- **NIH application ID:** 9925199
- **Project number:** 5R01AG054459-04
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Ai-Ling Lin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $571,376
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925199

## Citation

> US National Institutes of Health, RePORTER application 9925199, Multi-Modal MRI to Assess Alzheimer's Disease Prevention in an APOE4 Mouse Model (5R01AG054459-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9925199. Licensed CC0.

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