2010 Grants - Verbeek

ApoE and ApoJ in the Cerebrovascular Clearance of Amyloid-Beta Protein

Marcel M. Verbeek, Ph.D.
Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands

2010 Investigator-Initiated Research Grant

Beta-amyloid is a protein fragment that accumulates abnormally in the brain of persons with Alzheimer's disease, causes nerve cell toxicity, and forms amyloid plaques, one of the hallmarks of Alzheimer pathology. Evidence suggests that many cases of Alzheimer's disease may arise from dysfunction of the mechanisms that normally remove beta-amyloid from the brain. Indeed, ApoE and ApoJ are two proteins involved in removal of beta-amyloid from the brain, and variants of these proteins have been associated with an increased risk of Alzheimer's disease.

Marcel M. Verbeek, Ph.D., and colleagues are studying the mechanisms by which ApoE and ApoJ assist in the removal of beta-amyloid from the brain. They plan to study how beta-amyloid interacts with ApoE and ApoJ, and how this interaction is important for removal of beta-amyloid from the brain. Current evidence indicates that complexes of beta-amyloid and ApoE or ApoJ bind to cells, causing the cells to draw the complex inside and beginning the process of beta-amyloid removal. Dr. Verbeek's team will examine this process in detail, as well as the process by which beta-amyloid is transported out of the brain across the blood-brain barrier. These studies will address important questions about the molecular mechanisms leading to abnormal beta-amyloid deposits in the brain, and they may identify key targets for the development of drugs to prevent such deposits.