Fig. 2

LM11A-31 reduces AT8 tau pathology, tau phosphorylation and tau^K280 acetylation. a AT8 immunostaining in 9-month old untreated and treated Ntg and Tg mice (AT8, red; Nissl staining, green). Scale bar, 50 µm. b % of hippocampal area with AT8-positive immunostaining in post-treatment mice. For the total hippocampal region (HC total), significance determined using Kruskal–Wallis with Dunn’s post hoc multiple comparisons test. p values for the indicated comparisons are shown. For HC regions, ANOVA with Sidak’s post hoc multiple comparison testing; n = 8–13 mice per group. c–e Western blot analyses of sarkosyl-insoluble hippocampal lysates performed with the indicated antibodies. Primary p-tau bands of ~ 68 and 64 kDa (AT180, AT270) and an acetylated band (tau^K280) at ~ 40 kDa appear in Tg samples. f–h Densitometric quantitation of the combined two primary p-tau bands and the single tau^K280 band with p-values indicated. Statistical significance was determined using Kruskal–Wallis with post hoc Dunn’s testing (f, h) and ANOVA with post hoc Sidak’s testing (g); n = 6–11 mice per group with two independent western analyses averaged per animal. i–k Western blot analysis of soluble hippocampal synaptosome lysates performed with the indicated antibodies. p-Tau ~ 68/64 kDa (i, j) and acetyl-tau^K280 ~ 40 kDa (k) bands are detected. Bands at ~ 45 kDa in all four lanes (j) are due to prior probing of blots with actin antibody and persistence of signal. l–n Densitometric quantitation of combined ~ 68/64 kDa p-tau or ~ 40 kDa acetyl-tau^K280 signal with p-values for the indicated comparisons shown. Statistical significance was determined using ANOVA with post hoc Sidak’s multiple comparison testing; n = 6–11 mice per group, with two independent western blots averaged per animal