# Unraveling the mechanisms of microhemorrhages in cerebral amyloid angiopathy

> **NIH NIH R00** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $248,599

## Abstract

Project Summary / Abstract
Title project: “Unraveling the mechanisms of microhemorrhages in cerebral amyloid angiopathy; from ex vivo
MRI in humans to in vivo optics in mice”
Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid β (Aβ) in the walls of small
vessels in the brain, and is frequently observed at autopsy in the brains of Alzheimer’s disease (AD) patients.
CAA manifests itself clinically by the occurrence of widespread hemorrhagic lesions, including catastrophic
large hemorrhagic stroke. Moreover, CAA and CAA-related microhemorrhages - in the absence of major
bleeding - have increasingly been recognized as important contributors to cognitive impairment and dementia.
Finally, CAA has recently been assumed to increase the risk of developing microhemorrhages in anti-amyloid
immunotherapy, which is currently the only promising treatment in patients with AD. Yet, the underlying
mechanisms of hemorrhage formation are completely unknown. The proposed research responds to an urgent
need to study the interaction between small vessel disease and AD, a rapidly growing research area
recommended by the NIH for special emphasis. Preliminary observations suggest absence of vascular Aβ
deposits at the sites where hemorrhages had occurred. This suggests a complex interplay between Aβ and
vessel rupture and indicates that Aβ may not be directly harmful to vessels, but indirectly causes bleeding. The
applicant will determine which structural and functional alterations are involved at the level of the individual
vessels by combining state-of-the-art neuroimaging techniques and neuropathological examinations of human
brain tissue with cutting-edge optical imaging tools in living mice. The proposal builds on the applicant’s
strong background in ex vivo MRI and histopathology and her currently growing skills in multi-photon
microscopy in mice. The excellent scientific environment and numerous resources provided by the
Massachusetts General Hospital and Harvard Medical School, as well as the internationally recognized
leadership of the applicant’s mentors, and existing collaborations with experts in the field will be key to the
successful completion of the proposed research. This K99 award will be instrumental for the applicant to
strengthen her skillset, further grow in her scientific and professional qualities, and take the next steps towards
becoming an independent researcher. The proposed multi-modal approach will allow answering much needed
questions regarding the underlying mechanisms of hemorrhage formation, with the long-term goal to find
targets to prevent microhemorrhages in anti-amyloid therapies.

## Key facts

- **NIH application ID:** 10142789
- **Project number:** 4R00AG059893-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Susanne Janneke Van Veluw
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $248,599
- **Award type:** 4N
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10142789

## Citation

> US National Institutes of Health, RePORTER application 10142789, Unraveling the mechanisms of microhemorrhages in cerebral amyloid angiopathy (4R00AG059893-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10142789. Licensed CC0.

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