Figure 2.

Differential modification of tau in the PSD. (a) Western blot showing PSD95, tau, and α-synuclein levels in two different mice from a replicate cohort at each step of PSD fractionation. Full-length blots are presented in Supplementary Fig. 4. (b) Quantification of western blot signals. n = 8 mice, 5–6 months of age. Values were normalized to the average level of the respective protein in the cytosolic/membrane fraction (arbitrarily defined as 1.0). (c) Quantification of the five most common tau modifications in the PSD fraction relative to average levels in hippocampal and cortical whole lysate (arbitrarily defined as 1.0). Cohort B: n = 10 or 12 mice per group, 7–10 months of age (Supplementary Table 4). Because of site ambiguity, peptide sequences containing modified sites are indicated; di- and tri- denote doubly and triply modified peptides, respectively. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001 vs. whole lysate or as indicated by brackets (paired (b) or unpaired (c) t test with Holm correction). Welch's correction was applied in (c) to the analysis of peptides di-p386–404 and tri-p386–404 due to unequal variance. Cyt/Mem, cytosolic- and membrane-containing fraction; Cyt, cytosolic fraction; Mem, membrane fraction; Non-PSD, fraction remaining after PSD extraction; ns, not significant; RU, relative units; Syn, synaptosomal fraction. Quantitative values are means ± SEM. Some error bars in (b) are too small to see.