Figure 1.

Pathological implications of amyloid-β (Aβ), reactive oxygen species (ROS), and neuroinflammation and their role in potential therapeutic approaches for cerebral amyloid angiopathy (CAA) and Alzheimer’s disease (AD). Aβ produced in the brain aggregates to form fibrils, with intermediate oligomers being particularly cytotoxic. When Aβ is glycated, the products result in the persistence of cytotoxic oligomers. Dysfunction of the Aβ elimination system also results in Aβ accumulation in the brain. This Aβ-related pathology can result in the injury of cerebrovascular endothelial cells, VSMCs, and neurons, thereby promoting development and progression of CAA and AD. ROS and neuroinflammation are also cytotoxic factors closely implicated in CAA and AD pathogenesis. BACE1 inhibitors that inhibit Aβ production have been developed. Anti-glycation agents could reduce the accumulation of cytotoxic Aβ oligomers. Agents that facilitate the formation of mature fibers would also be effective. Taxifolin (TXN) has pleiotropic beneficial effects, including the suppression of the production and glycation of Aβ. The Aβ elimination system is also an effective target to reduce detrimental Aβ accumulation. Agents that facilitate the IPAD pathway or enhance ADAMTS13 function, antioxidants, and anti-inflammatory mediators may also exhibit protective effects against CAA and AD. Aβ, amyloid-β; AD, Alzheimer’s disease; ADAMTS13, a disintegrin and metalloprotease with thrombospondin type I motif, member 13; BACE1, β-site amyloid precursor protein cleaving enzyme-1; CAA, cerebral amyloid angiopathy; CSZ, cilostazol; IPAD, intramural peri-arterial drainage; OT, oxytocin; PUFAs, polyunsaturated fatty acids; ROS, reactive oxygen species; TwX, Twendee X; TXN, taxifolin.