Fig. 7

Schematic of the mechanisms by which HDL is hypothesized to protect cerebrovascular functions in AD. a In the absence of HDL, when Aβ peptides enter the vessel wall they are either taken up by SMC via LRP1 (1a) or become trapped in ECM, particularly when enriched in collagen-I (1b). 2) Accumulation of Aβ in the vessel wall induces endothelial activation and subsequent binding and transmigration of blood-derived circulating monocytes. 3) Astrocytes on the antelumen of penetrating arteries secret apoE that reduces collagen-I levels in the vascular wall. b in the presence of HDL, 4) HDL reduces monocyte binding via SR-BI (4a), whereas reduction of CAA is independent of SR-BI (4b). 5) HDL enters the cerebrovascular wall through undefined mechanisms and reduce Aβ uptake by SMC maybe by reducing LRP1 levels (5a), bind and remodel collagen-I fibres via HDL-apoE particles (5b) and form a complex with Aβ (5c), all of which increase luminal recovery of Aβ. 6) The reduction of CAA is specific to HDL