Fig. 1

TWD leads to T2D, memory impairment and increased number of dystrophic neurites in mice with AD-linked genetic backgrounds. a Weight of mice at age of 12 months (Two-way ANOVA). b Glucose tolerance test (GTT) results after 3 h fasting (Two-way ANOVA). c Serum glucose levels in GTT after 30 min of D-glucose injection (p = 0.001, Two-way ANOVA). d Representative liver sample image of TWD. Mice with TWD had significantly higher fatty liver score as compared to mice with STD (p < 0.001, Mann-Whitney). Black arrows indicate lipid vacuoles. Scale bar 20 μm. e Assessment of spontaneous activity (p < 0.001, Two-way ANOVA). f Passive avoidance test revealed impaired performance of mice with TWD as compared to mice with STD (diet effect, p = 0.02, Two-way ANOVA). Also, AD and tauopathy-associated transgenes impaired the performance (A+ = APPswe/PS1dE9; p < 0.001 and T+ = Tau P301L; p < 0.001, Two-way ANOVA). Three outliers were left out from statistical analysis (in brackets). g In five-day learning phase of Morris swim navigation test, mice with A+ transgene (APPswe/PS1dE9) (red lines) did not learn to find the platform as fast as mice without A+ transgene (blue lines, p = 0.002, Two-way ANOVA), while TWD and T+ transgene (Tau P301L) did not affect learning. h On day five, mice with A+ transgene spent significantly less time in platform zone (p = 0.001, Two-way ANOVA). Also, mice with TWD spent less time in platform zone as compared to mice with STD, but the difference did not reach statistical significance (p < 0.09, Two-way ANOVA). i A representative image of APPswe/PS1dE9 mouse coronal brain section used for assessing β-amyloid plaque load from lateral entorhinal cortex (LEC) and from dentate gyrus (DG) of hippocampus (HC). j Amyloid burden quantification in LEC, and k in HC. l A representative fluorescence microscope image of APPswe/PS1dE9 mouse coronal brain section showing AT8-positive dystrophic neurites around β-amyloid plaques. Scale bar = 10 μm. m Quantification of dystrophic neurites/plaque in LEC showing significant increase in TWD mice as compared to STD mice (p < 0.001). n Also, in HC number of dystrophic neurites per plaque was increased in TWD mice as compared to STD mice (p = 0.009). All results are shown as mean + SEM, behavioral tests: n = 5–7 mice/group, Two-way ANOVA, immunohistochemistry: n = 5–6 mice/group, 3 brain slices/mouse. Dystrophic neurites around β-amyloid plaques (diameter > 10 μM) were counted, Kruskal-Wallis H-test. AwTw = wild-type, AwT+ = Tau P301L, A + Tw = APPswe/PS1dE9, A + T+ = APPswe/PS1dE9 x Tau P301L