A $1.5 million grant has been awarded to University of Rhode Island neuroscientist William Van Nostrand to investigate one of the most dangerous and least understood vascular complications associated with aging and Alzheimer’s disease: cerebral amyloid angiopathy, or CAA. The funding forms part of a $9 million, five-year international research program supported by the Leducq Foundation. Known as TRAFFIC, or the Translational Framework for Innovation in Cerebral Amyloid Angiopathy, the initiative brings together researchers from the United States and Europe to clarify how CAA begins, identify biological signals that reveal the disease at an early stage, and discover potential targets for treatment.
CAA develops when amyloid-beta, a protein strongly associated with Alzheimer’s disease, accumulates abnormally within the walls of small and medium-sized blood vessels in the brain. Under healthy conditions, amyloid-beta is continuously cleared from brain tissue through cellular and vascular waste-removal systems. When these processes become impaired, the protein can build up in vessel walls, gradually disrupting their structure. The affected vessels may lose elasticity and become fragile, leaving them vulnerable to leakage or rupture. As a result, CAA can cause microscopic brain bleeds, larger hemorrhagic strokes, and progressive damage to neural networks involved in memory and cognition.
The disease is common among older adults and is frequently found in the brains of people with Alzheimer’s disease, although the two conditions are not identical. CAA can exist without the characteristic memory loss associated with Alzheimer’s, and its vascular effects may create a distinct set of clinical risks. Small areas of bleeding, known as cerebral microbleeds, can accumulate over time and may be detected using specialized magnetic resonance imaging. However, imaging findings are not always sufficient to determine how active or advanced the disease is. Researchers still lack reliable early-stage biomarkers—measurable biological indicators that can identify the disease before substantial vascular injury has occurred.
“Despite the prevalence of the disease, there are no reliable early-stage biomarkers and disease-modifying therapies currently do not exist,” said Van Nostrand, co-executive director of URI’s George & Anne Ryan Institute for Neuroscience and a professor in the Department of Pharmaceutical and Biomedical Sciences in the URI College of Pharmacy. The absence of targeted therapies is particularly concerning because treatments that influence blood clotting or reduce the risk of ischemic stroke may carry additional dangers in patients whose vessels are already weakened by amyloid deposits. A clearer understanding of the molecular events that make these vessels bleed could help clinicians distinguish risk and guide safer interventions.
Van Nostrand’s laboratory will focus on why CAA develops in some individuals and how specific risk factors increase the likelihood of bleeding. The team will use an animal model developed at URI that reproduces important features of human CAA. Such models allow researchers to examine the disease over time and investigate processes that cannot be observed directly in living patients. Scientists can track the formation of amyloid deposits, measure changes in vessel integrity, and test how inflammation, impaired clearance, genetic factors, or other biological stresses influence the transition from vascular accumulation to hemorrhage.
A central question is how amyloid-beta transforms a blood vessel from a functioning component of the brain’s circulation into a source of injury. Deposits may alter the smooth muscle cells and other structural elements that help vessels regulate blood flow and withstand pressure. They may also disturb communication between blood vessels and surrounding brain cells, weaken the blood-brain barrier, and activate inflammatory responses. These changes could make vessels more permeable and less capable of repairing everyday damage. By examining these mechanisms in detail, the URI researchers hope to identify stages in the disease process at which intervention might prevent irreversible vascular failure.
The TRAFFIC network will connect Van Nostrand’s work with studies conducted at Harvard Medical School, Vanderbilt University Medical Center, Vall d’Hebron Research Institute in Spain, and Otto von Guericke University Magdeburg in Germany. The project will be coordinated by Andreas Charidimou of Boston University and Marcel Verbeek of Radboud University Medical Center in the Netherlands. This transatlantic structure is designed to combine expertise in experimental neuroscience, clinical neurology, neuroimaging, molecular biology, and biomarker development. Comparing findings across laboratories and patient populations may help determine which biological signatures are consistently linked to CAA progression and bleeding risk.
The investigators will also examine how CAA relates to the brain’s waste-clearance systems. These pathways help move soluble proteins and other metabolic byproducts away from neural tissue, including through routes associated with the walls of small blood vessels. If clearance is disrupted, amyloid-beta may remain in the brain longer and become more likely to accumulate in vessel walls. Van Nostrand has been involved since 2024 in a separate Leducq Foundation project studying the breakdown of brain waste-clearance mechanisms that contribute to the biological processes underlying CAA. Insights from that work are expected to complement the new TRAFFIC studies.
The project is scheduled to begin in January 2027. Its long-term aim is to move CAA research beyond describing vascular damage toward predicting and preventing it. By identifying early molecular changes, clarifying why some amyloid-laden vessels rupture while others do not, and testing potential points of therapeutic intervention, the researchers hope to establish a foundation for disease-modifying treatments. The effort could also improve the interpretation of brain imaging and help physicians assess hemorrhage risk in older adults and people with Alzheimer’s disease. “Support from these highly competitive and prestigious transatlantic networks will reveal new insights into the disease, paving the way for better diagnosis and development of disease-modifying therapies,” Van Nostrand said.
Subject of Research: Cerebral amyloid angiopathy, amyloid-beta accumulation in brain blood vessels, vascular fragility, brain hemorrhage risk, biomarkers, and disease-modifying therapies.
Article Title: International Research Network Targets the Vascular Damage Behind Cerebral Amyloid Angiopathy
Web References:
https://ryaninstitute.uri.edu/
https://web.uri.edu/pharmacy
https://www.fondationleducq.org/network/translational-framework-for-innovation-in-cerebral-amyloid-angiopathy-traffic-26cvd03/
URI neuroscientist is part of $8M grant for U.S. and European consortium on brain clearance research
Image Credits: Photo courtesy William Van Nostrand
Keywords: Cerebral amyloid angiopathy, CAA, amyloid-beta, Alzheimer’s disease, brain hemorrhage, cerebral microbleeds, neuroscience, biomarkers, blood-brain barrier, brain waste clearance, Leducq Foundation, TRAFFIC, University of Rhode Island.
Tags: aging and cerebrovascular healthaging-related brain healthAlzheimer’s disease pathologyAlzheimer’s disease vascular complicationsamyloid-beta protein accumulationbrain vessel fragility and hemorrhagecerebral amyloid angiopathy researchearly detection of CAAinternational neurodegenerative disease fundingneural network damage from vascular diseaseneurovascular damage in dementiatargeting CAA for Alzheimer’s treatment
