# Mechanisms of vasomotion-mediated perivascular clearance in cerebral amyloid angiopathy

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $615,131

## Abstract

Project Summary / Abstract
Title project: “Mechanisms of vasomotion-mediated perivascular clearance in cerebral amyloid angiopathy”
The blood vessels in the brain play an important role in facilitating clearance of metabolic waste products.
Impaired perivascular clearance of amyloid β (Aβ) has been implicated in the pathophysiology of cerebral
amyloid angiopathy (CAA) and Alzheimer’s disease. However, fundamental unknows including the
directionality and major driving forces of perivascular clearance remain, which has hampered the development
of therapeutic strategies aimed at targeting the perivascular waste clearance system. Moreover, experimental
observations in mice have remain largely unexplored in the human brain. Prior work from the applicant
uncovered a role for vasomotion – slow spontaneous oscillations of arterioles generated by vascular smooth
muscle cells (SMCs) – as a major driving force for perivascular clearance. This project will further zoom in on
vasomotion and test the novel hypothesis that targeting vascular SMCs may provide an attractive approach to
enhance vasomotion and thereby facilitate perivascular Aβ clearance. This project will use CAA as a model
disease to test this hypothesis, as CAA is characterized by the gradual deposition of vascular Aβ, impaired
perivascular clearance, SMC degeneration, and vascular dysfunction. The aims of this project are to further
unravel the physiological basis of vasomotion-mediated perivascular clearance, to determine the effect of
vascular Aβ accumulation on vasomotion and clearance, to explore the potential of enhancing low frequency
arteriolar oscillations as an intervention strategy to successfully clear Aβ from the brain, and to measure the
coupling between low frequency hemodynamics and fluid flow in the human brain. We will use a translational
approach, utilizing optical imaging techniques in awake mice coupled with direct optogenetic stimulation of
vascular SMCs, as well as fast functional MRI in human individuals with and without CAA. Successful
completion of these aims will improve our understanding of the physiological basis of vasomotion-mediated
perivascular clearance and provide much needed proof-of-concept data to support the potential of modulating
low frequency arteriolar oscillations as an early intervention strategy to promote Aβ clearance from the brain.

## Key facts

- **NIH application ID:** 10518909
- **Project number:** 1R01NS128790-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Susanne Janneke Van Veluw
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $615,131
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10518909

## Citation

> US National Institutes of Health, RePORTER application 10518909, Mechanisms of vasomotion-mediated perivascular clearance in cerebral amyloid angiopathy (1R01NS128790-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10518909. Licensed CC0.

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