Progression of cerebral amyloid angiopathy: a pathophysiological framework

Lancet Neurol. 2023 Jul;22(7):632-642. doi: 10.1016/S1474-4422(23)00114-X. Epub 2023 May 23.


Cerebral amyloid angiopathy, which is defined by cerebrovascular deposition of amyloid β, is a common age-related small vessel pathology associated with intracerebral haemorrhage and cognitive impairment. Based on complementary lines of evidence from in vivo studies of individuals with hereditary, sporadic, and iatrogenic forms of cerebral amyloid angiopathy, histopathological analyses of affected brains, and experimental studies in transgenic mouse models, we present a framework and timeline for the progression of cerebral amyloid angiopathy from subclinical pathology to the clinical manifestation of the disease. Key stages that appear to evolve sequentially over two to three decades are (stage one) initial vascular amyloid deposition, (stage two) alteration of cerebrovascular physiology, (stage three) non-haemorrhagic brain injury, and (stage four) appearance of haemorrhagic brain lesions. This timeline of stages and the mechanistic processes that link them have substantial implications for identifying disease-modifying interventions for cerebral amyloid angiopathy and potentially for other cerebral small vessel diseases.

Publication types

  • Review

MeSH terms

  • Amyloid beta-Peptides
  • Animals
  • Brain / pathology
  • Cerebral Amyloid Angiopathy* / complications
  • Cerebral Hemorrhage / complications
  • Cognitive Dysfunction* / pathology
  • Mice


  • Amyloid beta-Peptides