Abstract
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.
Highlights
Sporadic cerebral amyloid angiopathy (CAA) is characterized by progressive accumulation of cerebrovascular amyloid β (Aβ) in the walls of leptomeningeal arteries and cortical capillaries in the brain
We found that hematomas often occurred in the subcortex in very elderly patients with intracerebral hemorrhage (ICH), and a high prevalence of CAA was strongly implicated in ICH occurrence [7]
(3T susceptibility-weighted imaging (SWI)), and we found that Cortical superficial siderosis (cSS) was associated with a strictly lobar Cerebral microbleeds (CMBs) location, which indicated a close relationship between CAA and cSS [20]
Summary
Sporadic cerebral amyloid angiopathy (CAA) is characterized by progressive accumulation of cerebrovascular amyloid β (Aβ) in the walls of leptomeningeal arteries and cortical capillaries in the brain. We previously investigated the locations of hematomas in very elderly patients (≥80 years old) with ICHs and compared them with those of patients with. We found that hematomas often occurred in the subcortex in very elderly patients with ICH, and a high prevalence of CAA was strongly implicated in ICH occurrence [7]. This review aims to: summarize the clinical, pathological, and radiological features of CAA; describe current. 2021, 22, x FOR PEER REVIEW management strategies for CAA; discuss proposed mechanisms of formation of CAA; and to: summarize the clinical, pathological, and radiological features of CAA; describe curclarify the CAA-related molecules that may be therapeutic targets. Rent management strategies for CAA; discuss proposed mechanisms of formation of CAA; and clarify the CAA-related molecules that may be therapeutic targets
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