# Brain pericyte contractility, cerebral blood flow and blood-brain barrier integrity are impaired by normal aging and Alzheimer's disease amyloid-beta and are dependent on p75NTR

> **NIH NIH R00** · UNIVERSITY OF SOUTH ALABAMA · 2021 · $249,000

## Abstract

PROJECT SUMMARY/ ABSTRACT
Neurovascular dysfunction has been linked to Alzheimer’s disease (AD) evolution in experimental, imaging,
pathological, and epidemiological studies. These key findings have led to an emerging ‘neurovascular
hypothesis’ of AD, which holds that cerebrovascular dysfunction contributes to the onset and progression of
cognitive decline. There is growing appreciation and strong evidence that neurovascular uncoupling, cerebral
blood flow (CBF) reductions and dysregulation, and breakdown of the blood-brain barrier (BBB), including the
loss of pericytes, are early events in the AD pathophysiological cascade. Pericytes are mural cells on
capillaries that are critical for the maintenance of the BBB, and have recently been implicated in the regulation
of CBF. Importantly, pericytes deteriorate and the BBB degrades in AD. Based on our preliminary findings we
hypothesize that pericytes are contractile cells that regulate capillary diameter and thereby CBF, and BBB
integrity, and that this pericyte regulation is impaired in normal aging and in the presence of Aβ40 and Aβ42 via
p75NTR pathway. To test this hypothesis, I will use cutting-edge approaches including in vivo two-
photon/confocal brain vascular imaging to assess pericyte contractility, capillary diameter, CBF changes and
BBB integrity. Brain tissue analysis will also be performed. I will determine if brain pericytes retain contractility,
properly regulate CBF, and maintain BBB integrity in normal aging and in the presence of Aβ40 and Aβ42 (AIM
1/ K99). Also, I will determine if normal aging and Aβ40 and Aβ42 impair brain BBB integrity via p75NTR (AIM 2/
R00). Understanding how pericytes regulate CBF and BBB integrity in normal aging and AD and the
involvement and potential of p75NTR as a therapeutic target for AD is timely and important. This K99/R00
grant is essential for my success in becoming an impactful tenure-track assistant professor because it
provides me training in an essential technique to investigate neurovascular dynamics for future
studies, and also will provide professional training in improving oral presentation and grant writing
skills.

## Key facts

- **NIH application ID:** 10236555
- **Project number:** 5R00AG058780-04
- **Recipient organization:** UNIVERSITY OF SOUTH ALABAMA
- **Principal Investigator:** Amy R Nelson
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2018-07-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10236555

## Citation

> US National Institutes of Health, RePORTER application 10236555, Brain pericyte contractility, cerebral blood flow and blood-brain barrier integrity are impaired by normal aging and Alzheimer's disease amyloid-beta and are dependent on p75NTR (5R00AG058780-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10236555. Licensed CC0.

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