# leptomeningeal vessel wall enhancement as an early pathophysiological marker of cerebral amyloid angiopathy

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $462,000

## Abstract

Project Summary / Abstract
Title project: “leptomeningeal vessel wall enhancement as an early pathophysiological marker of cerebral
amyloid angiopathy”
Cerebral amyloid angiopathy (CAA) is a significant contributor to cognitive impairment and dementia and a
leading cause of intracerebral hemorrhage (ICH) in older individuals. CAA is characterized by the
accumulation of Aβ in the walls of cortical and leptomeningeal vessels. It has been suggested that vascular Aβ
deposition involves a self-reinforcing cycle of reduced vascular reactivity and impaired perivascular clearance
of Aβ from the brain, eventually resulting in vessel wall breakdown and the formation of hemorrhages.
Currently, CAA patients are only recognized during the late stages of the disease by the detection of
hemorrhages on brain MRI. Bleeding from leptomeningeal vessels, recognized as superficial siderosis on
MRI, has recently emerged as one of the strongest predictors for future symptomatic ICH. However, there are
currently no in vivo tools available to identify vessels at risk for superficial siderosis. In this proposal, we aim to
determine the potential of contrast agent leakage as an early detection strategy to predict future sites of
bleeding. We will utilize high-resolution heavily T2-weighted post-contrast fluid-attenuated inversion recovery
(FLAIR) MRI after intravenous gadolinium administration to detect leakage from individual leptomeningeal
vessels at the surface of the brain. Leveraging the dataset acquired in this patient population, we will further
assess the clearance of gadolinium after focal leakage into perivascular spaces to determine the feasibility of
mapping perivascular clearance routes in humans non-invasively. The results will inform the design of
future mechanistic studies looking at perivascular clearance dynamics in CAA and Alzheimer’s disease. The
proposal builds on the applicants’ international leadership in CAA, their strong background in advanced
neuroimaging, and translational research program involving ex vivo MRI-guided neuropathology and in vivo
two-photon imaging in mouse models. Combined with the world-class resources and international
collaborations with experts in the field to perform advanced image processing, the proposed set of experiments
will likely yield much needed answers regarding the early pathophysiology in CAA. Novel insights resulting
from this project may also yield promising new targets to prevent vascular cognitive impairment and dementia
in the elderly.

## Key facts

- **NIH application ID:** 10108743
- **Project number:** 1R21AG070363-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Susanne Janneke Van Veluw
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $462,000
- **Award type:** 1
- **Project period:** 2020-09-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10108743

## Citation

> US National Institutes of Health, RePORTER application 10108743, leptomeningeal vessel wall enhancement as an early pathophysiological marker of cerebral amyloid angiopathy (1R21AG070363-01). Retrieved via AI Analytics 2026-06-03 from https://api.ai-analytics.org/grant/nih/10108743. Licensed CC0.

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