Genetics and molecular pathogenesis of sporadic and hereditary cerebral amyloid angiopathies

Acta Neuropathol. 2009 Jul;118(1):115-30. doi: 10.1007/s00401-009-0501-8. Epub 2009 Feb 19.

Abstract

In cerebral amyloid angiopathy (CAA), amyloid fibrils deposit in walls of arteries, arterioles and less frequently in veins and capillaries of the central nervous system, often resulting in secondary degenerative vascular changes. Although the amyloid-beta peptide is by far the commonest amyloid subunit implicated in sporadic and rarely in hereditary forms of CAA, a number of other proteins may also be involved in rare familial diseases in which CAA is also a characteristic morphological feature. These latter proteins include the ABri and ADan subunits in familial British dementia and familial Danish dementia, respectively, which are also known under the umbrella term BRI2 gene-related dementias, variant cystatin C in hereditary cerebral haemorrhage with amyloidosis of Icelandic-type, variant transthyretins in meningo-vascular amyloidosis, disease-associated prion protein (PrP(Sc)) in hereditary prion disease with premature stop codon mutations and mutated gelsolin (AGel) in familial amyloidosis of Finnish type. In this review, the characteristic morphological features of the different CAAs is described and the implication of the biochemical, genetic and transgenic animal data for the pathogenesis of CAA is discussed.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / complications
  • Alzheimer Disease / therapy
  • Amyloid beta-Peptides / metabolism
  • Amyloidosis / complications
  • Amyloidosis / genetics
  • Animals
  • Brain / blood supply*
  • Brain / metabolism
  • Brain / pathology
  • Brain / physiopathology
  • Cerebral Amyloid Angiopathy / genetics*
  • Cerebral Amyloid Angiopathy / pathology*
  • Cerebral Amyloid Angiopathy / physiopathology
  • Cerebral Amyloid Angiopathy / therapy
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / genetics
  • Cystatin C / genetics
  • Dementia / complications
  • Dementia / genetics
  • Disease Models, Animal
  • Genetic Predisposition to Disease
  • Humans
  • Immunotherapy
  • Mutation
  • Prealbumin / metabolism
  • Prion Diseases / complications

Substances

  • Amyloid beta-Peptides
  • Cystatin C
  • Prealbumin