Insights into the pathogenesis and pathogenicity of cerebral amyloid angiopathy

Front Biosci (Landmark Ed). 2009 Jan 1;14(12):4778-92. doi: 10.2741/3567.

Abstract

Amyloid-beta (Abeta) cerebral amyloid angiopathy (CAA) affects most Alzheimer's disease (AD) patients and ~30% of otherwise-normal elderly people. APOE epsilon 4 is a major risk factor for CAA in AD. Neurons are probably the source of the vascular Abeta. CAA develops when Abeta is deposited in the vessel walls along or across which it normally passes into the CSF and bloodstream. Vascular deposition is facilitated by factors that increase Abeta40:Abeta42, impede perivascular passage of Abeta or raise its concentration. The levels of some Abeta-degrading enzymes are reduced in AD patients with CAA. However, angiotensin-converting enzyme activity is increased and may act via angiotensin II to increase transforming growth factor beta1, a potent inducer of ECM synthesis. CAA is a cause of intracerebral haemorrhage and cerebral ischaemic damage. In AD, neuritic degeneration is accentuated around Abeta-laden vessels. Rarely, CAA is associated with angiitis. The balance between parenchymal and cerebrovascular degradation of Abeta, and regulation of perivascular extracellular matrix production, are likely to be key determinants of Abeta distribution and pathogenicity within the brain.

Publication types

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

MeSH terms

  • Cerebral Amyloid Angiopathy / etiology*
  • Cerebral Amyloid Angiopathy / genetics
  • Genetic Predisposition to Disease
  • Humans
  • Risk Factors