Efficacy of MW071 against Aβ- and tau-oligomer induced defects in LTP and memory. A) Perfusion with MW071 (10μM) rescues the LTP defect in hippocampal slices treated with 200 nM Aβ- or 50 nM tau-oligomers. MW071 alone did not affect potentiation. ANOVA for repeated measures between groups: F(1,19) = 27.85, p < 0.0001 vehicle versus Tau; F(1,18) = 24.74, p < 0.0001 vehicle versus Aβ; F(1,22) = 10.37, p = 0.0039 Tau versus Tau + MW071; F(1,19) = 7.222, p = 0.0146 Aβ versus Aβ+ MW071; (F(1, 18) = 0.0082, p = 0.93 vehicle versus MW071.Vehicle: N = 10 (5 males, 5 females), MW071: N = 10 (5 males, 5 females), Aβ: N = 10 (5 males, 5 females), Aβ+ MW071: N = 11 (5 males, 6 females), Tau: N = 11 (6 males, 5 females), Tau + MW071: N = 13 (7 males, 6 females). B, C) MW071 protects mice against the impairment of spatial (B) and associative memory (C) by infusion of 200 nM Aβ- or 500 nM tau-oligomers into dorsal hippocampi bilaterally, while MW071 alone does not affect performance. RAWM: ANOVA for repeated measures among all (day 2): F(5,65) = 6.158, p < 0.0001. One-way ANOVA for block 10: F(5,65) = 8.552, p < 0.0001; Bonferroni’s p < 0.0001 vehicle versus Aβ; p = 0.0006 vehicle versus Tau; p = 0.0013 Aβ versus Aβ + MW071; p = 0.0108 Tau versus Tau + MW071 and p = 1 vehicle versus MW071. Vehicle: N = 10 (5 males, 5 females), MW071: N = 13 (6 males, 7 females), Aβ: N = 12 (6 males, 6 females), Aβ+ MW071: N = 12 (6 males, 6 females), Tau: N = 11 (5 males, 6 females), Tau+ MW071: N = 13 (7males, 6 females). Fear conditioning: Baseline: One-way ANOVA F(5,60) = 1.217, p = 0.3122, 24 h Contextual: One-way ANOVA F(5,60) = 9.391, p < 0.0001; Bonferroni p = 0.0002 vehicle versus Aβ; p < 0.0001 vehicle versus Tau; p = 0.0043 Aβ versus Aβ+ MW071; p = 0.028 Tau versus Tau + MW071; p = 1 vehicle versus MW071. Vehicle: N = 9 (5 males, 4 females), MW071: N = 10 (5 males, 5 females), Aβ: N = 13 (7 males, 6 females), Aβ+ MW071: N = 11 (6 males, 5 females), Tau: N = 11 (5 males, 6 females), Tau+ MW071: N = 12 (6 males, 6 females).