# Molecular and Physiological Mechanisms of Hypertensive Cerebral Microangiopathy

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $797,572

## Abstract

Project Summary
The small vessel diseases of the brain are responsible not only for ischemic and hemorrhagic strokes but also
vascular cognitive impairment and dementia, major sources of disability and death in older adults. Despite the
fact that hypertensive cerebral small vessel disease (HTN-cSVD) is the most common type of brain
microangiopathy, the mechanisms linking this condition to brain tissue injury and cognitive impairment are
unknown, therefore no specific preventive or therapeutic method targeting physiopathological processes exist.
We propose a systematic, multidisciplinary analysis of the mechanisms underlying HTN-cSVD related
cerebrovascular dysfunction, impaired perivascular clearance and their connections to brain damage including
pathological amyloid/tau protein accumulations. The unique patient cohort is composed of nondemented
survivors of a hypertensive intracerebral hemorrhage (HTN-ICH), a well-characterized indicator of severe HTN-
cSVD. Specific experiments are designed to compare advanced physiological MRI measures of vascular
reactivity and vascular compliance between patients with HTN-ICH and healthy older adults in addition to
delineating the relationship of vascular dysfunction with established markers of HTN-cSVD [Specific Aim (SA)
1a and 1b]. These experiments are geared towards testing the hypothesis that HTN-cSVD causes vascular
dysfunction which in turn might mediate larger-scale brain tissue injury. The second set of experiments will test
the potential effects of HTN-cSVD on accumulation of amyloid and tau proteins in the brain, answering the key
question of whether decreased clearance related to small vessel dysfunction might contribute to the
accumulation of these pathological hallmarks of Alzheimer’s Disease (SA 2a and 2b). The third set of studies
will analyze the effects of vascular, structural and molecular changes on cognition using both cross-sectional
and longitudinal assessments (SA 3a and 3b). The proposal builds on a wide range of cutting-edge
methodologic advances such as multimodal physiological imaging with 7T ultrahigh field functional MRI,
molecular Aß and tau PET imaging, and the use of state-of-the-art structural imaging markers of HTN-cSVD.
Successful completion of the proposed highly translational experiments will determine the physiological and
molecular mechanisms of brain tissue damage related to HTN-cSVD and the impact of these processes on
cognition. These results will represent a major step towards understanding the contributions of the most
common vascular brain disease (HTN-cSVD) to dementia, thereby allowing design of clinical trials aimed at
preserving or enhancing vascular function using validated imaging markers of the vascular physiology.

## Key facts

- **NIH application ID:** 10051722
- **Project number:** 1R01NS114526-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Mahmut Edip Gurol
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $797,572
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10051722

## Citation

> US National Institutes of Health, RePORTER application 10051722, Molecular and Physiological Mechanisms of Hypertensive Cerebral Microangiopathy (1R01NS114526-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10051722. Licensed CC0.

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