Current Management and Therapeutic Strategies for Cerebral Amyloid Angiopathy

Int J Mol Sci. 2021 Apr 8;22(8):3869. doi: 10.3390/ijms22083869.


Cerebral amyloid angiopathy (CAA) is characterized by accumulation of amyloid β (Aβ) in walls of leptomeningeal vessels and cortical capillaries in the brain. The loss of integrity of these vessels caused by cerebrovascular Aβ deposits results in fragile vessels and lobar intracerebral hemorrhages. CAA also manifests with progressive cognitive impairment or transient focal neurological symptoms. Although development of therapeutics for CAA is urgently needed, the pathogenesis of CAA remains to be fully elucidated. In this review, we summarize the epidemiology, pathology, clinical and radiological features, and perspectives for future research directions in CAA therapeutics. Recent advances in mass spectrometric methodology combined with vascular isolation techniques have aided understanding of the cerebrovascular proteome. In this paper, we describe several potential key CAA-associated molecules that have been identified by proteomic analyses (apolipoprotein E, clusterin, SRPX1 (sushi repeat-containing protein X-linked 1), TIMP3 (tissue inhibitor of metalloproteinases 3), and HTRA1 (HtrA serine peptidase 1)), and their pivotal roles in Aβ cytotoxicity, Aβ fibril formation, and vessel wall remodeling. Understanding the interactions between cerebrovascular Aβ deposits and molecules that accumulate with Aβ may lead to discovery of effective CAA therapeutics and to the identification of biomarkers for early diagnosis.

Keywords: amyloid β; cerebral amyloid angiopathy; cerebral microbleeds; intracerebral hemorrhage; proteomic analyses; superficial siderosis.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers
  • Cerebral Amyloid Angiopathy / diagnosis*
  • Cerebral Amyloid Angiopathy / etiology
  • Cerebral Amyloid Angiopathy / therapy*
  • Cerebral Hemorrhage / diagnostic imaging
  • Cerebral Hemorrhage / pathology
  • Clinical Decision-Making
  • Disease Management
  • Disease Susceptibility
  • Fluorescent Antibody Technique
  • Humans
  • Immunohistochemistry
  • Proteome
  • Proteomics / methods


  • Biomarkers
  • Proteome