Fig. 5. Impaired Aβ efflux from the brain induced by amyloid-forming human amylin secreted from the pancreas.

a Western blot analyses of brain tissue Aβ in WT and HIP rats (n = 4–5 males/group; age 15–16-months) with rat Aβ₄₀ and APP/PS1 rat brain homogenate used as positive controls for Aβ immunoreactivity signal. b Estimated brain Aβ efflux through immunoprecipitation and Western blot analyses of Aβ in plasma and brain homogenates from WT and HIP rats (similar to those in a), with APP/PS1 rat brain homogenate used as positive control for Aβ immunoreactivity signal. c Proposed amylin action on the Aβ transport across the BBB. d Confocal microscopy and STORM analysis of amylin in brain microvessels isolated from HIP (n = 47 microvessels) and WT (n = 21 microvessels) rats (n = 3 males/group; age 15–16 months). Confocal microscopy analysis of serial sections from HIP rat brains stained with Thioflavin S (Thio S) or amylin (e) and with the lipid peroxidation marker 4-HNE or amylin (f) (n = 3 males similar to those in d). Western blot analysis of P-gp (g) and LRP1 (h) in brain microvessel lysates from HIP and WT rats (n = 5–7 males/group similar to those in a), and in brain microvascular ECs incubated with human amylin. Data are means ± SEM.