Sporadic cerebral amyloid angiopathy (2011)

Author(s): Attems J, Jellinger K, Thal DR, Van Nostrand W

    Abstract: Cerebral amyloid angiopathy (CAA) may result from focal to widespread amyloid-beta protein (A beta) deposition within leptomeningeal and intracortical cerebral blood vessels. In addition, pericapillary A beta refers to A beta depositions in the glia limitans and adjacent neuropil, whereas in capillary CAA A beta depositions are present in the capillary wall. CAA may cause lobar intracerebral haemorrhages and microbleeds. Hypoperfusion and reduced vascular autoregulation due to CAA might cause infarcts and white matter lesions. CAA thus causes vascular lesions that potentially lead to (vascular) dementia and may further contribute to dementia by impeding the clearance of solutes out of the brain and transport of nutrients across the blood brain barrier. Severe CAA is an independent risk factor for cognitive decline. The clinical diagnosis of CAA is based on the assessment of associated cerebrovascular lesions. In addition, perivascular spaces in the white matter and reduced concentrations of both A beta(40) and A beta(42) in cerebrospinal fluid may prove to be suggestive for CAA. Transgenic mouse models that overexpress human A beta precursor protein show parenchymal A beta and CAA, thus corroborating the current concept of CAA pathogenesis: neuronal A beta enters the perivascular drainage pathway and may accumulate in vessel walls due to increased amounts and/or decreased clearance of A beta, respectively. We suggest that pericapillary A beta represents early impairment of the perivascular drainage pathway while capillary CAA is associated with decreased transendothelial clearance of A beta. CAA plays an important role in the multimorbid condition of the ageing brain but its contribution to neurodegeneration remains to be elucidated.

      • Date: 11-01-2011
      • Journal: Neuropathology and Applied Neurobiology
      • Volume: 37
      • Issue: 1
      • Pages: 75-93
      • Publisher: Wiley-Blackwell Publishing Ltd.
      • Publication type: Article
      • Bibliographic status: Published

      Professor Johannes Attems
      Professor of Neuropathology, Honorary Consultant Pathologist