Cerebral amyloid angiopathies: a pathologic, biochemical, and genetic view

J Neuropathol Exp Neurol. 2003 Sep;62(9):885-98. doi: 10.1093/jnen/62.9.885.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cerebral Amyloid Angiopathy* / genetics
  • Cerebral Amyloid Angiopathy* / metabolism
  • Cerebral Amyloid Angiopathy* / pathology
  • Humans
  • Molecular Sequence Data
  • Mutation*