Cerebral amyloidosis, amyloid angiopathy, and their relationship to stroke and dementia

Cerebral amyloid angiopathy (CAA) is the common term used to define the deposition of amyloid in the walls of medium- and small-size leptomeningeal and cortical arteries, arterioles and, less frequently, capillaries and veins. CAA is an important cause of cerebral hemorrhages although it may also lead to ischemic infarction and dementia. It is a feature commonly associated with normal aging, Alzheimer disease (AD), Down syndrome (DS), and Sporadic Cerebral Amyloid Angiopathy. Familial conditions in which amyloid is chiefly deposited as CAA include hereditary cerebral hem-orrhage with amyloidosis of Icelandic type (HCHWA-I), fa-milial CAA related to Aβ variants, including hereditary cere-bral hemorrhage with amyloidosis of Dutch origin (HCHWA-D), the transthyretin-related meningocerebrovascular amyloi-dosis of Hungarian and Ohio kindreds, the gelsolin-related spinal and cerebral amyloid angiopathy, familial PrP-CAA, and the recently described chromosome 13 familial dementia in British and Danish kindreds. This review focuses on the various molecules and genetic variants that target the cere-bral vessel walls producing clinical features related to stroke and/or dementia, and discusses the potential role of amyloid in the mechanism of neurodegeneration. 1