Cerebral amyloid angiopathy as one of the most common types of small vessel diseases of the brain

Small vessel diseases of the brain (SVD) encompass a range of pathologies affecting small arteries, capillaries, and venules, and are a common cause of ischemic strokes and cerebral hemorrhages. One of the most prevalent forms of SVD is cerebral amyloid angiopathy (CAA), characterized by the deposition of amyloid in the vessel walls, leading to their weakening and subsequent hemorrhages. This process is frequently associated with neurodegenerative disorders, particularly Alzheimer’s disease. The development of CAA is driven by multiple pathogenic mechanisms, including endothelial dysfunction, disruption of the blood-brain barrier, and neuroinflammation mediated by activated macrophages. Nitric oxide, produced by the endothelium, plays a crucial role in regulating vascular tone; its reduction serves as a marker of endothelial dysfunction, resulting in vasoconstriction and ischemia. Concurrently, blood-brain barrier disruption promotes plasma extravasation, impairs the transport of oxygen and nutrients, and stimulates neuroinflammatory responses. CAA is a multifactorial disease, and recent studies suggest that vascular oxidative stress induced by macrophages is also a significant contributor to its progression. Oxidative stress caused by the NOX2 enzyme in macrophages damages blood vessels and enhances amyloid accumulation, leading to impaired cerebral circulation and disease progression. This article reviews the key mechanisms underlying the pathogenesis of SVD and CAA, emphasizing the critical roles of endothelial dysfunction and neuroinflammation in their development. The findings may contribute to the development of novel therapeutic strategies aimed at correcting endothelial dysfunction and modulating inflammatory responses, thereby offering new prospects for the treatment of CAA and other SVD.