Cerebral Amyloid Angiopathy: Emerging Evidence for Novel Pathophysiology and Pathogenesis

Cerebral amyloid angiopathy (CAA) is cerebrovascular amyloid deposition being classified into several types according to the amyloid protein involved. Of these, sporadic amyloid β-protein (Aβ)-type CAA is most commonly found in older individuals and in patients with Alzheimer’s disease (AD). Cerebral blood vessels affected with CAA are associated with functional and pathological changes (CAA-associated vasculopathies), leading to development of hemorrhagic disorders (lobar intracerebral macrohemorrhage, cortical microhemorrhage, and cortical superficial siderosis/focal convexity subarachnoid hemorrhage), ischemic disorders (white matter disease and cortical microinfarcts), and inflammatory vascular disorders, i.e., CAA-associated inflammation/angiitis; these CAA-related disorders are characterized by unique clinical features and imaging and cerebrospinal fluid abnormalities, contributing to a clinical diagnosis of CAA without brain biopsy. In this review, we particularly focus on topics with emerging evidence for novel pathophysiology and pathogenesis of CAA. They include CAA-related cognitive impairment and neurodegeneration, and CAA-related inflammation and similar disorders associated with Aβ immunotherapies for AD. Furthermore, recent studies indicated that Aβ pathologies, including CAA, would be transmissible in humans as well as experimental settings. Better understanding of mechanisms underlying pathophysiology and pathogenesis of CAA would lead to new strategies for interventions for CAA.