Cerebral hemorrhage, a devastating subtype of stroke, is often caused by hypertension and cerebral amyloid angiopathy (CAA). Pathological evidence of CAA is detected in approximately half of all individuals over the age of 70 and is associated with cortical microinfarcts and cognitive impairment. The underlying pathophysiology of CAA is characterized by accumulation of pathogenic amyloid β (Aβ) fragments of amyloid precursor protein in the cerebral vasculature. Vascular deposition of Aβ damages the vessel wall, results in blood-brain barrier (BBB) leakiness, vessel occlusion or rupture, and leads to hemorrhages and decreased cerebral blood flow that negatively affects vessel integrity and cognitive function. Currently, the main hypothesis surrounding the mechanism of CAA pathogenesis is that there is an impaired clearance of Aβ peptides, which includes compromised perivascular drainage as well as dysfunction of BBB transport. Also, the immune response in CAA pathogenesis plays an important role. Therefore, the mechanism by which Aβ vascular deposition occurs is crucial for our understanding of CAA pathogenesis and for the development of potential therapeutic options.
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