Damaged Blood Vessels Loaded with Amyloid Worsen Cognitive Impairment in Alzheimer’s Disease

A team of researchers at Weill Cornell Medical College has discovered that amyloid peptides are harmful to the blood vessels that supply the brain with blood in Alzheimer’s disease — thus accelerating cognitive decline by limiting oxygen-rich blood and nutrients. In their animal studies, the investigators reveal how amyloid-ß accumulates in blood vessels and how such accumulation and damage might be ultimately prevented.

Their study, published in the Feb. 4 online edition of the Proceedings of the National Academy of Sciences (PNAS), is the first to identify the role that the innate immunity receptor CD36 plays in damaging cerebral blood vessels and promoting the accumulation of amyloid deposits in these vessels, a condition known as cerebral amyloid angiopathy (CAA).

Importantly, the study provides the rational bases for targeting CD36 to slow or reverse some of the cognitive deficits in Alzheimer’s disease by preventing CAA.

"Our findings strongly suggest that amyloid, in addition to damaging neurons, also threatens the cerebral blood supply and increases the brain’s susceptibility to damage through oxygen deprivation," says the study’s senior investigator, Dr. Costantino Iadecola, the Anne Parrish Titzell Professor of Neurology at Weill Cornell Medical College and director of the Brain and Mind Research Institute at Weill Cornell Medical College and NewYork-Presbyterian Hospital. "If we can stop accumulation of amyloid in these blood vessels, we might be able to significantly improve cognitive function in Alzheimer’s disease patients. Furthermore, we might be able to improve the effectiveness of amyloid immunotherapy, which is in clinical trials but has been hampered by the accumulation of amyloid in cerebral blood vessels."

Mounting scientific evidence shows that changes in the structure and function of cerebral blood vessels contribute to brain dysfunction underlying Alzheimer’s disease, but no one has truly understood how this happens until now.