CEREBRAL AMYLOID ANGIOPATHY AND ALZHEIMER'S DISEASE

Abstract

Deposition of ß-amyloid peptide in the cerebral arterioles, small arteries, and capillaries, designated as cerebral amyloid angiopathy (CAA), is a nearly universal accompanying feature of Alzheimer's Disease (AD). Mild CAA appears to have little effect on vessels, but more advanced stages are associated with vascular rupture and intracerebral hemorrhage as well as with impaired vascular function, nonhemorrhagic brain lesions, and cognitive impairment. The Religious Orders Study, for example, demonstrated worse perceptual speed and episodic memory-independent of AD pathology and other covariates-among the one-fifth of individuals with moderate-to-very severe CAA. These findings suggest that AD and CAA might frequently act in concert to produce mixed dementia. A second link between AD and CAA are the striking similarities between the vasogenic edema-amyloid related imaging abnormalities (ARIA-E) seen in AD immunotherapy trials and the spontaneous syndrome of CAA-related inflammation. CAA-related inflammation appears to be driven by cerebrospinal production of anti-amyloid autoantibodies, indicating a shared mechanism for the two syndromes. Despite concerns about antibody-mediated adverse events, the key pathogenic role of ß-amyloid in CAA makes anti-amyloid immunotherapy a rational therapeutic approach for this largely untreatable disease.