# Multiscale optical characterization of cerebrovascular structure, function and oxygen utilization in a novel mouse model of sporadic Alzheimer's disease

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $410,656

## Abstract

PROJECT SUMMARY/ABSTRACT
Our long-term goal is to develop neurotechnologies that measure optical biomarkers indicative
of early onset of Alzheimer’s Disease (AD) or treatment response. AD is a leading cause of
adult disability and the most common cause of dementia in the United States. Despite the
tremendous worldwide investment in addressing AD, therapeutic approaches shown to have
efficacy in mouse models have failed in human clinical trials with late-onset sporadic AD. The
overall objective of this application is to study the time course of cerebral blood flow (CBF) and
cerebral metabolic rate of oxygen (CMRO2) in development of late-onset sporadic AD
pathology. We will address key issues such as age-related changes in cerebral microvascular
structure (using optical clearing) and function (using optical measurements of CBF and CMRO2)
applied to two AD mouse models: the well-established 3xTg model pioneered by co-I LaFerla,
and the novel LaFerla hAβ-KI model of LOAD pathogenesis. We propose use of three
innovative concepts to study in vivo development of cerebrovascular dysfunction and
development of AD pathology: 1) an animal model that recapitulates late-onset sporadic AD
(LOAD pathogenesis, 2) a new in vivo optical imaging platform capable of absolute
measurements of CBF and metabolism, and 3) ex vivo whole-brain visualization of brain
structures with use of optical clearing and light-sheet microscopy. Our Specific Aims are to 1)
Assess cross-sectional and longitudinal relationship among CBF, CMRO2, cerebrovascular
pulsatility, and flow-metabolism coupling dynamics, in wild-type, 3xTg, and hAβ-Ki mouse
models; and 2) Validate vascular imaging biomarkers with microvascular structural parameters,
neuroinflammation markers, and Aβ. Completion of these studies is expected to contribute to
our knowledge on the relationship between neurovascular and metabolic alterations and AD
pathogenesis. This innovative approach is expected to pave the way to enhanced
understanding of age-related AD pathogenesis, and ultimately to informed development of new
therapeutic strategies that target preservation of neurovascular health. We expect to establish a
quantitative imaging platform that, due to its relatively low cost, can be readily utilized by other
researchers worldwide

## Key facts

- **NIH application ID:** 9877250
- **Project number:** 1R21AG066000-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** BERNARD CHOI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $410,656
- **Award type:** 1
- **Project period:** 2020-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9877250

## Citation

> US National Institutes of Health, RePORTER application 9877250, Multiscale optical characterization of cerebrovascular structure, function and oxygen utilization in a novel mouse model of sporadic Alzheimer's disease (1R21AG066000-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9877250. Licensed CC0.

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