# The Microvasculature in Alzheimer’s Disease: Viable Microvessels for Studies of Brain Endothelial and Glycocalyx Health

> **NIH NIH R03** · UNIVERSITY OF WASHINGTON · 2022 · $155,500

## Abstract

ABSTRACT/SUMMARY
 Brain microvasculature is altered in Alzheimer’s Disease (AD), but there are few methods to
examine cellular processes in living tissue. Viable brain microvessels (MV) can be isolated from
whole brain tissue of subjects undergoing rapid autopsy (<12 hours post mortem) in the UW
Neuropathology (NP) Core. The donor subjects in the UW NP Core have a clinical diagnosis of
dementia or no dementia, and all brain specimens undergo extensive neuropathologic
assessment. This proposal utilizes innovative methods to rapidly obtain and maintain viable brain
MV for a minimum of 5 days in supportive liquid media under standard tissue culture conditions,
which affords a unique opportunity to study the microvasculature in brains with and without AD.
 Many aspects of MV structure and composition contribute to interactions that are relevant to
AD. For this R03, the focus is on the luminal surface and the 2 components that are the initial
interface between the brain and the systemic circulation: 1) the brain microvascular endothelial
cell (BEC), and 2) the glycocalyx, a dynamic gel-like layer of extracellular matrix (ECM) that lines
the luminal surface of BEC.
 The following 2 hypotheses will be tested. First, MV from those with dementia have similar
BEC-specific viability and overall metabolic activity, but increased prevalence of senescent BEC
relative to MV from those without dementia. Second, MV from those with dementia have greater
glycocalyx shedding, which reflects increased degradative enzymes, relative to MV from those
without dementia. Samples and outcome measures will be initially examined based on the clinical
diagnosis of dementia or no dementia, and then re-classified according to subsequent detailed
neuropathologic criteria.
 Aim 1 will define how BEC from dementia and no dementia MV specimens differ with respect
to outcome measures of BEC-specific viability, overall metabolic activity, and BEC senescence.
Aim 2 will determine how the glycocalyx from dementia and no dementia MV differ in de novo
synthesis of ECM and markers of ECM degradation. Studies of glycocalyx will focus on heparan
sulfate proteoglycans (HSPGs) and hyaluronan (HA). Knowledge gained will provide the
foundation for perturbation/intervention experiments that are feasible, and have therapeutic
implications for the mitigation of deleterious MV changes with dementia.

## Key facts

- **NIH application ID:** 10352021
- **Project number:** 1R03AG075397-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** MAY J REED
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $155,500
- **Award type:** 1
- **Project period:** 2022-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10352021

## Citation

> US National Institutes of Health, RePORTER application 10352021, The Microvasculature in Alzheimer’s Disease: Viable Microvessels for Studies of Brain Endothelial and Glycocalyx Health (1R03AG075397-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10352021. Licensed CC0.

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