# Admin Supplement: Longitudinal multimodal mapping to decipher the neurovascular impact of microinfarcts

> **NIH NIH R01** · RICE UNIVERSITY · 2022 · $395,443

## Abstract

Project Summary
This application is an Alzheimer's-focused administrative supplement to the parent grant titled “Longitudinal
multimodal mapping to decipher the neurovascular impact of microinfarcts”, NINDS R01-NS109361, PI: Lan
Luan. The primary goal of the parent grant is to understand the neural and hemodynamic impact of individual
and cumulative cerebral microinfarcts in healthy aged mice. To achieve this goal, we have developed a
technological platform for inducing microinfarcts with fine control of time and location, and for comprehensively
tracking and evaluating neural and hemodynamic activity in vivo at high spatial resolutions and over a time
course of several months. The goal of this supplement is to leverage these existing tools towards mouse models
of Alzheimer's disease (AD) in order to decipher how AD amyloid pathology interacts with cortical microinfarcts
to affect cerebral blood flow and neuronal activity. This topic is particularly relevant to the pathogenesis of AD
as researchers and clinicians have increasingly recognized the importance of mixed pathologies, e.g. the
coexistence of neurodegenerative and cerebrovascular disease pathologies, as critical factors in the
development of AD and other dementias. However, the extent to which cortical microinfarcts and abnormalities
in cerebral blood flow modulate AD pathogenesis and affect neural function is poorly understood; how local
amyloid affects the neural response to microinfarcts is undefined. We propose to use the APPNL-G-F knock-in
mouse model of AD which develop amyloid (A) pathology, neuroinflammation, and memory impairment in an
age-dependent manner. This mouse model expresses amyloid precursor protein (APP) in the native
spatiotemporal pattern of endogenous APP, avoiding overexpression artifacts of earlier transgenic mice. We will
use two-dimensional arrays of nanoelectronic threads (NETs), currently the most flexible and biocompatible
neural electrodes, for chronic intracortical recordings. Neural recording will be combined with concurrent optical
imaging to induce microinfarcts, map and quantify cerebral blood flow (CBF), and track and quantify the
accumulation of Aplaques. We will 1) comprehensively evaluate longitudinal changes in cortical neural activity
and CBF as A amyloidosis progresses; and 2) determine how microinfarcts affect the local development of
amyloid plaques and neural activity, and how amyloid accumulation affects local neural and hemodynamic
response to microinfarcts. By realizing, for the first time, simultaneous mapping and longitudinal tracking of
amyloid deposition, neural activity, and CBF with controlled occurrence of microinfarcts in a state-of-the-art AD
mouse model, our result will define how AD pathology influences neural-hemodynamic interactions and how
microinfarcts complicate the disease progression of AD.

## Key facts

- **NIH application ID:** 10499182
- **Project number:** 3R01NS109361-04S2
- **Recipient organization:** RICE UNIVERSITY
- **Principal Investigator:** Lan Luan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $395,443
- **Award type:** 3
- **Project period:** 2019-02-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499182

## Citation

> US National Institutes of Health, RePORTER application 10499182, Admin Supplement: Longitudinal multimodal mapping to decipher the neurovascular impact of microinfarcts (3R01NS109361-04S2). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10499182. Licensed CC0.

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