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. Author manuscript; available in PMC: 2020 Jul 24.
Published in final edited form as: Nature. 2019 Oct 23;574(7780):686–690. doi: 10.1038/s41586-019-1688-z

Fig. 1: HSD increases tau phosphorylation and insoluble tau.

Fig. 1:

a, HSD increases AT8 and RZ3 levels. (CTX: AT8, ND/HSD n=8/9, *p<0.0001 vs ND; RZ3, ND/HSD n=12/11, *p<0.0001 vs ND; HIPP: AT8, ND/HSD n=9/9, *p<0.0001 vs ND; RZ3, ND/HSD n=9/9, *p=0.0011 vs ND, two-tailed unpaired t-test). b, HSD increases neuronal AT8 immunoreactivity in the piriform cortex (size bar=500 μm; 100 μm in inset). Representative images from ND and HSD mice (n=5/group). c, Time course of the neocortical increase in AT8 and RZ3 (AT8, 4 weeks: ND/HSD n=4/5, *p=0.0116 vs ND; 8 weeks: ND/HSD n=9/8, *p=0.0066 vs ND; 24 weeks: ND/HSD n=8/9, *p=0.0152 vs ND; 36 weeks: ND/HSD n=4/5, *p=0.0087 vs ND; RZ3, 4 weeks: ND/HSD n=4/5, *p=0.0097 vs ND; RZ3, 8 weeks: ND/HSD n=7/8, *p=0.0084 vs ND; 24 weeks: ND/HSD n=8/9, *p=0.0135 vs ND; 36 weeks: ND/HSD n=4/5, *p=0.0204 vs ND, two-tailed unpaired t-test). d, HSD induces deficits in recognition memory (Diet: *p<0.0001, Time: *p=0.0002; 8 weeks: ND/HSD n=8/11; 12 weeks: ND/HSD n=16/12; 24 weeks: ND/HSD n=14/13 mice/group, two-way ANOVA and Tukey’s test). e, HSD induces deficits in spatial memory (Diet: *p=0.0048, Time: *p<0.0001; ND/HSD n=13/12, two-way RM ANOVA and Bonferroni’s test; Primary Latency Day 5, ND/HSD n=13/12, *p=0.0031 vs ND, two-tailed unpaired t-test). f, Neocortical and hippocampal levels of AT8 correlate with spatial learning impairment (AT8 CTX: BM r=0.4491, *p<0.0001, n=84; NOR r=−0.2621, *p=0.0188, n=80; AT8 HIPP: BM r=0.2073, *p=0.0462, n=93; NOR r=−0.2915, *p=0.0053, n=90, Pearson’s correlation coefficient). g, HSD increases levels of insoluble tau (Western blotting) extracted in RIPA and FA after 12 weeks of treatment (CTX: RIPA, ND/HSD n=7/10, *p=0.0032 vs ND; FA, ND/HSD n=8/7, *p=0.0146 vs ND; HIPP: RIPA, ND/HSD n=7/9, *p=0.0418 vs ND; FA, ND/HSD n=7/9, *p=0.0494 vs ND, two-tailed unpaired t-test). h, HSD increases levels of insoluble tau (electrochemiluminescence method) (CTX: RIPA, ND/HSD n=11, *p=0.0050 vs ND; FA, ND/HSD n=14/11, *p=0.0028 vs ND; HIPP: RIPA, ND/HSD n=6/8, *p=0.0380 vs ND; FA, ND/HSD n=7/8, *p=0.0037 vs ND, two-tailed unpaired t-test). I: HSD shifts tau from the RAB fraction to the less soluble RIPA and FA fractions (CTX: ND/HSD n=9/8, RAB, p=0.4234 vs ND, RIPA, p=0.5414 vs ND, FA, *p=0.0325 vs ND; HIPP: ND/HSD n=5/6, RAB, p=0.2468 vs ND, RIPA, p=0.3290 vs ND, FA, *p=0.0152 vs ND, two-tailed unpaired t-test). For gel source data see supplementary figure 1. Data are expressed as mean±SEM.