Current Management and Therapeutic Strategies for Cerebral Amyloid Angiopathy

Cerebral amyloid angiopathy (CAA) is characterized by accumulation of amyloid beta (A beta) in walls of leptomeningeal vessels and cortical capillaries in the brain. The loss of integrity of these vessels caused by cerebrovascular A beta 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 A beta cytotoxicity, A beta fibril formation, and vessel wall remodeling. Understanding the interactions between cerebrovascular A beta deposits and molecules that accumulate with A beta may lead to discovery of effective CAA therapeutics and to the identification of biomarkers for early diagnosis.

Automated summary

Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid beta (Aβ) in brain vessels, leading to vessel fragility, hemorrhages, and neurological symptoms. The pathogenesis of CAA is not fully understood, but recent advances in mass spectrometric methodology have identified potential key molecules associated with CAA. Understanding the interactions between cerebrovascular Aβ deposits and these molecules may lead to the development of effective CAA therapeutics.