# Viable Microvessels for the Study of the Microvasculature in Alzheimer's Disease > **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2021 · $194,375 ## Abstract The brain microvasculature is altered in Alzheimer’s disease (AD), but there are few methods for studying cellular mechanisms 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 Core. Recently, this technique has been adapted such that MV in a 3 dimensional (3D) matrix have extended viability to at least 10 days (d) post-isolation, and scalability to generate numerous replicates for studies. Subjects are well characterized for the clinical diagnosis of dementia or no dementia, and all specimens undergo subsequent extensive neuropathologic assessment. The blood-brain barrier (BBB) of the MV is the interface that regulates movement of substances into and out of the brain. The principle cellular components of the BBB are brain endothelial cells (BEC), pericytes, and astrocyte foot processes. Pericytes are closely apposed to BEC and support maintenance of BBB properties. Importantly, BEC and pericytes contribute to, and are affected by, both the glycocalyx and basement membrane (BM) extracellular matrix (ECM), which is altered significantly by AD. Studies of MVs in 3D culture systems allow for spatial analysis of relevant cellular and protein components. Extended MV viability allows for evaluation of interventions and potential mechanisms that impact MV health. The goal is to establish these MV to obtain foundational information on microvascular changes in AD. There are 2 specific aims, with each subject’s MV serving as their own baseline control. In Aim 1, the hypothesis that MV from age and sex matched subjects, with and without the clinical diagnosis of dementia, will maintain fidelity (cellular viability, levels of BBB functional proteins, and ECM components) to their initially isolated MV for prolonged periods (up to 10d) in 3D will be tested. All specimens will have analysis of their donor en bloc brain specimens, to determine whether MV in 3D will maintain the cellular, BBB proteins, and ECM phenotype of their brain MV that are examined histologically in situ. Pericyte loss is accelerated in the MV of brain regions affected by AD neuropathology. A lack of pericytes is known to result in changes in BBB function, but effects on ECM are not well studied. Aim 2 will determine the effects of pericyte loss on MV derived from brains of subjects without dementia on the BBB ECM. In Aim 2, the hypothesis that pericyte loss results in alterations in ECM content, such that MV ECM from those without dementia will resemble MV ECM from those with dementia, will be tested. Aims 1 and 2 will be performed concurrently to optimize utilization of brain specimens. Taken together, data from these Aims will advance the study of brain MV in AD to create a platform for additional interventional work. ## Key facts - **NIH application ID:** 10286231 - **Project number:** 1R21AG073676-01 - **Recipient organization:** UNIVERSITY OF WASHINGTON - **Principal Investigator:** MAY J REED - **Activity code:** R21 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2021 - **Award amount:** $194,375 - **Award type:** 1 - **Project period:** 2021-08-15 → 2023-05-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10286231 ## Citation > US National Institutes of Health, RePORTER application 10286231, Viable Microvessels for the Study of the Microvasculature in Alzheimer's Disease (1R21AG073676-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10286231. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*