To view an abstract, select an author from the vertical list on the left.
2014 Grants - Grutzendler
The Role of Angiophagy in Alzheimer’s Disease Pathology
Jaime Grutzendler, M.D.
Yale University School of Medicine
New Haven, Connecticut
2014 Investigator-Initiated Research Grant: Role of Vascular Metabolic Risk Factors in the Pathogenesis of Alzheimer’s Disease and Related Dementia
According to recent studies, damage to tiny blood vessels called “microvessels” in the brain may contribute to increased risk of developing Alzheimer’s disease. This microvascular damage may be linked to specific dementia-related brain changes, including memory loss and the clumping of a protein fragment called beta-amyloid into amyloid plaques, a hallmark of Alzheimer’s disease. Yet the study of microvessels in dementia is limited, partly because imaging technologies have been unable to visualize them with sufficient clarity in living brains.
Jaime Grutzendler, M.D., and colleagues have been studying microvascular function in the brain using newly-refined, high-resolution imaging methods. As a result of their work, they identified a novel process by which the body prevents microvascular damage. In this process, which they call “angiophagy,” vessel-clogging debris are engulfed by the cells that line the vessels and the clog is removed, restoring normal blood flow. The researchers also found that beta-amyloid, a protein fragment that plays an important role in the development of Alzheimer’s disease, may hinder angiophagy by interacting with certain types of debris. This interaction may promote the accumulation of beta-amyloid around blood vessels leading to blood vessel damage known as cerebral amyloid angiopathy (CAA), a condition linked to nerve cell damage, memory loss and the development of Alzheimer’s disease.
For their current studies, Dr. Grutzendler and colleagues will extend their studies using mice engineered to develop CAA in conjunction with a novel brain imaging technology to track the movement of debris in their animals’ tiniest blood vessels. The researchers will determine if there are certain cell types, or certain areas of the brain that are particularly vulnerable to CAA-related damage. They will also examine how immune cells in the brain called microglia help to clear debris and beta-amyloid from blood vessels. The results of their work could shed new light on how CAA develops in the brain — and how microvessel pathology may affect the risk of developing Alzheimer’s disease.