# Understanding cellular architecture of the neurovascular unit and its function in the whole mouse brain

> **NIH NIH R01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2021 · $194,408

## Abstract

Abstract
Alzheimer’s disease (AD) is characterized by steep cognitive decline especially affecting learning and memory
and has become a prominent public health concern driven by an increasing aging population. Prior research
pinpointed accumulations of toxic cellular wastes such as amyloid beta (Aβ) as a primary pathophysiological
hallmark in AD. Vascular disorders, which affect the brain’s ability to clear metabolic wastes and supply energy
to neurons, have long been implicated in AD pathology. Microvessels which form complex networks provide
large surface areas as a main interface between blood supply and brain tissues. Moreover, pericytes ensheathe
microvessels allowing them to regulate blood flow and permeability. Emerging evidence suggests that the
degeneration of microvessels and pericytes has been frequently observed in AD patients and animal models of
AD. Moreover, Aβ accumulation and degeneration of vascular networks in AD occur in different brain regions at
different rates across the whole brain. While strong evidence of the harmful interactions between Aβ
accumulation and neurovascular function in AD exists, whether microvessel and pericyte injury occurs prior to
Aβ accumulation and how interactions of Aβ with microvessels and pericytes change over time across different
brain regions remains unclear. To discover this and more fully understand brain regional vulnerabilities, temporal
affectations, and their consequences to brain function, we need to examine the quantitative distribution of
microvessels and pericytes upon Aβ insults in relation to AD related behavioral changes. Therefore, we propose
a two part hypothesis to examine the brain-wide changes of microvessels and pericyte populations in correlation
with the emergence of Aβ accumulation in 5xFAD mice. SA1 will focus on the hypothesis that degeneration of
microvessels occurs prior to Aβ accumulation and cognitive deficit while SA2 will test a hypothesis that
degeneration of pericytes precede Aβ accumulation as the disease progresses. Both methods will utilize cutting-
edge clearing and 3D immunolabeling, high-resolution light sheet fluorescent microscopy imaging, and advanced
computational analysis to generate a first of its kind vascular/pericyte whole brain atlas in an AD mouse model
with further analysis to resolve the interactions of microvessels/pericytes with Aβ paired with behavioral testing
to assess cognitive deficits at the presymptomatic and early symptomatic stages of AD.

## Key facts

- **NIH application ID:** 10401994
- **Project number:** 3R01NS108407-04S1
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Yongsoo Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $194,408
- **Award type:** 3
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401994

## Citation

> US National Institutes of Health, RePORTER application 10401994, Understanding cellular architecture of the neurovascular unit and its function in the whole mouse brain (3R01NS108407-04S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10401994. Licensed CC0.

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