The role of amyloid beta clearance in cerebral amyloid angiopathy: more potential therapeutic targets

Aβ can be transported bi-directionally through BBB by multiple receptors. In normal conditions the transportation of Aβ can be mediated by multiple receptors in endothelium. After binding to ApoE or α2M (α2-microglobulin) Aβ can be transported by LRP1 or it can be transported by LRP2 after binding to ApoJ (clusterin). Some other receptors also mediate Aβ efflux, such as ABC transporter, insulin-sensitive transporter and ANP-sensitive transporter. There’s only little Aβ influx mediated by RAGE and OATP. In addition Aβ can be transported to perivascular spaces and eliminated through perivascular drainage. In CAA pathological condition, there’s a change in the transporter profile of the BBB, with the efflux receptors decreasing and the influx receptors increasing, leading to the decrease of Aβ clearance and its deposition on the vessel wall. Consequently components changes of cerebrovascular basement membrane as well as the weakness of perivascular drainage results in the aggregation of Aβ in blood vessels aggregating CA