Aging, Cerebral Amyloid Angiopathy, and Amyloid Beta Clearance

Summary

Alzheimer’s disease, the most common form of dementia, is characterized by fibrillar deposits of amyloid beta (Aβ) protein in brain tissue and cerebral blood vessels. The complex molecular mechanisms involved in the formation and accumulation of these deposits are not well understood; however, the brain’s failure to remove Aβ is increasingly recognized as a central element in the disease pathogenesis. Our preliminary data indicate that the action of brain enzymes and impaired clearance of the resulting degradation fragments via the blood and cerebrospinal fluid should not be overlooked as crucial contributors. The central focus of this project is how brain Aβ removal is additionally influenced by aging and by the dysfunction of the cerebral microvasculature. Using state of the art methodologies and genetically engineered mouse models with severely compromised cerebral blood vessels, this project will provide a better understanding how the brain degrades and removes Aβ in health and disease, an approach that will likely identify new targets for pharmacologic intervention.