Cerebral amyloid angiopathy (CAA) is a common cause of brain hemorrhage in older adults and a major contributor to cognitive impairment and dementia. However, the disease remains challenging to diagnose accurately and no targeted therapeutic options are currently available. To advance scientific knowledge of CAA, the Leducq Foundation has awarded nine million dollars to an international project led by Boston University (US) and Radboud University Medical Center in Nijmegen (the Netherlands), with the participation of the Neurovascular Diseases group at the Vall d’Hebron Research Institute (VHIR).

CAA is characterized by the abnormal buildup of amyloid-beta protein in the walls of the brain’s blood vessels. Over time, vascular amyloid accumulation can damage and ultimately weaken the vessels, increasing a person’s risk of hemorrhagic stroke and contributing to cognitive decline.

Although CAA is found in the brains of more than half of patients with hemorrhagic stroke and in the majority of patients with Alzheimer’s disease, much remains unknown about how the condition develops and progresses.

The aim of the TRAFFIC project (Translational Framework For Innovation in Cerebral Amyloid Angiopathy) i is to improve understanding of critical steps in the pathobiology and the early detection and diagnosis of CAA, an essential step toward enabling earlier interventions and developing future therapies. The international research team will combine advanced brain imaging with new molecular biomarkers and innovative experimental models. By studying brain scans, body fluids and tissues, and clinical data from patients worldwide, the researchers aim to uncover how CAA develops, progresses, and causes damage to the brain’s blood vessels, including inflammatory forms of the disease (CAA-related inflammation and amyloid-related imaging abnormalities).

At Vall d’Hebron, preclinical models of the disease will be used to better understand its pathophysiological mechanisms. “We will contribute to this project by bringing the knowledge and expertise that our group has acquired over many years of research in cerebral amyloid angiopathy. We are one of the few centres in Spain specialising in the study of this disease, which allows us to contribute well-established expertise to the project”, explains Dr. Mar Hernández Guillamon, principal investigator of the Neurovascular Diseases group at VHIR and project lead at Vall d’Hebron, the only Spanish centre participating in the network.

By integrating clinical, molecular, and experimental research, the TRAFFIC network aims to generate critical insights into the mechanisms of CAA, improve diagnostic strategies, lay the foundation for future therapies, and build a lasting international community of CAA researchers.

Research and training in cerebral amyloid angiopathy

In addition to the research project itself, a core component of the initiative is training the next generation of CAA scientists. Through mentorship, funding, and hands-on opportunities across participating laboratories, the network will equip early-career researchers with the skills and collaborative experience needed to advance the field.

“CAA is among the most common pathologies affecting the aging brain, yet fundamental unanswered questions about how the disease develops and progresses continue to limit clinical progress, including our ability to diagnose it accurately and early”, says Dr. Antreas Charidimou, who leads the project from Boston University. “By bringing together complementary expertise across clinical, molecular, and experimental research, TRAFFIC is designed to address these gaps while fostering the next generation of CAA investigators. We hope this network will have a lasting impact on the field and ultimately improve care for patients at risk of brain bleeds and cognitive decline”, he adds.

“Over the past 10--20 years we have learned a lot about CAA, and this has evolved clinical diagnostic criteria. However, these [criteria] clearly fall short in identifying the entire spectrum of CAA, since they are solely focused on neuroimaging signs”, says Dr. Marcel Verbeek of Radboud University Medical Center. “These are typically late-stage signs, whereas we know that molecular biomarkers will be abnormal earlier on. So, that is why we aim to work towards a new framework for diagnostics, incorporating the newest insights into molecular mechanisms”, he concludes.

The TRAFFIC network brings together seven centres that are among the leading institutions in CAA research. In addition to Drs. Charidimou and Verbeek and Dr. Mar Hernández Guillamon, the project includes the teams of Dr. Matthew Schrag at Vanderbilt University Medical Center, Dr. Steven Greenberg at Harvard Medical School, Dr. Stephanie Schreiber at Otto von Guericke University Magdeburg, and Dr. William Van Nostrand at the University of Rhode Island. The project will begin in January and will run for five years.

Support from the Leducq Foundation

This research project is funded by the Leducq Foundation. The Foundation is an international organisation that awards grants with the mission of improving human health through international efforts to combat cardiovascular disease and stroke.

To this end, the Leducq Foundation promotes the International Networks of Excellence Program in Cardiovascular and Neurovascular Research, which supports basic, translational and clinical research through international collaboration on cardiovascular and neurovascular diseases. The programme’s primary objective is to foster exceptional and innovative scientific research by bringing together international teams of investigators with complementary expertise and resources to work collaboratively on a common problem.