Amyloid deposition can take place in the walls of arteries, arterioles, and, less often, capillaries and veins of the central nervous system, a phenomenon known as
cerebral amyloid angiopathy (CAA). The major clinicopathological manifestations of CAA include
cerebral hemorrhage, ischemic lesions, and
dementia. CAA may be classified according to the
amyloid protein deposited. In the most common form, sporadic CAA, and in CAA related to sporadic
Alzheimer disease (AD). A beta deposition is characteristic. CAA can also be severe in variants of familial AD caused by mutations of the
amyloid-beta precursor protein or
presenilin-1 genes in which deposition of A beta variants and/or wild-type A beta occurs. Other
amyloid proteins involved in familial CAAs include 1) the mutant
cystatin C (ACys) in
hereditary cerebral hemorrhage with amyloidosis of Icelandic type, 2) variant transthyretins (ATTR) in meningo-vascular
amyloidoses, 3) mutated
gelsolin (AGel) in
familial amyloidosis of Finnish type, 4) disease-associated
prion protein (PrP(Sc)) in a variant of the Gerstmann-Sträussler-Scheinker syndrome, and 5) ABri and ADan in CAAs observed in the recently described BRI2 gene-related
dementias, familial British
dementia and
familial Danish dementia, respectively. This review addresses issues related to the correlation between morphology, biochemistry, and genetics, and briefly discusses both the pathogenesis and animal models of CAAs.