Figure 1.

A, Continuous ICV Aβ₄₂ infusion for 1 week increased FLNA association with α7nAChR, and twice-daily intraperitoneal injections of PTI-125 for 2 weeks significantly reduced this interaction. Synaptosomes prepared from prefrontal cortex and hippocampus of treated mice were immunoprecipitated with immobilized anti-FLNA, and α7nAChR levels in the immunoprecipitates were detected by Western blot (WB) using an α7nAChR-specific antibody. B, ICV Aβ₄₂ infusion also increased FLNA association with TLR4, detected in the same anti-FLNA immunoprecipitates with a TLR4-specific antibody. C, Aβ₄₂ strongly promoted tau phosphorylation at Ser²⁰², Thr²³¹, and Thr¹⁸¹, and PTI-125 significantly reduced phosphorylation at all three sites. Levels of tau protein phosphorylated at each site were measured in the immunoprecipitates of an anti-tau antibody that did not distinguish its phosphorylation state by Western blotting with specific antibodies separately recognizing each tau phosphoepitope. Blots (inset) were analyzed by densitometric quantitation. n = 7 or 8. *p < 0.01 vs sham, vehicle; #p < 0.01 vs Aβ₄₂, vehicle.