Sporadic cerebral amyloid angiopathy: pathology, clinical implications, and possible pathomechanisms

Acta Neuropathol. 2005 Oct;110(4):345-59. doi: 10.1007/s00401-005-1074-9. Epub 2005 Sep 17.

Abstract

Cerebral amyloid angiopathy (CAA) was observed for the first time nearly 100 years ago and systematically described in 1938. It is a common finding in elderly individuals, defined by beta-amyloid peptide (Abeta) depositions in cerebral blood vessels, and associated with Alzheimer's disease (AD). A variety of genetic mutations cause hereditary forms of CAA; in this review, however, only the sporadic variant of CAA is considered. In CAA, Abeta depositions primarily occur in the abluminal portion of the tunica media, and with increasing severity all layers of the blood vessel wall are infiltrated and an additional spread of Abeta into the surrounding neuropil may be seen (i.e., dyshoric changes). CAA is most pronounced in the occipital lobe and its distribution is usually patchy. The relationship between CAA and AD is poorly understood; however, low positive correlations between the severity of both CAA and AD pathology have been observed. CAA is a frequent cause of (warfarin-associated) intracerebral hemorrhage, and the diagnosis of probable CAA-related hemorrhage can be made during life with high accuracy. Both APOE-epsilon4 and APOE-epsilon2 are risk factors for CAA, while only APOE-epsilon2 increases the risk for hemorrhage in CAA. Although the role of CAA as an independent risk factor for cognitive decline is unclear, severe CAA is likely to lower the threshold for clinically overt dementia in neurodegenerative diseases. As for the origin of Abeta in CAA, it may be both produced by smooth muscle cells (vessel wall) and derived from neurons in the course of perivascular drainage.

Publication types

  • Historical Article

MeSH terms

  • Amyloid beta-Peptides / metabolism*
  • Apolipoproteins E / genetics
  • Cerebral Amyloid Angiopathy / etiology*
  • Cerebral Amyloid Angiopathy / history
  • Cerebral Amyloid Angiopathy / metabolism
  • Cerebral Amyloid Angiopathy / pathology*
  • History, 19th Century
  • History, 20th Century
  • Humans
  • Myocytes, Smooth Muscle / metabolism
  • Neurons / metabolism
  • Risk Factors

Substances

  • Amyloid beta-Peptides
  • Apolipoproteins E