Methylation stoichiometries of soluble tau proteins purified from cognitively normal middle age (CNMA) and elderly (CNE) cases, and of aggregated tau from AD cases were determined by targeted metabolomics analysis. Each circular point represents methylation stoichiometry in a single biological replicate in units of mol residue/mol tau protein, whereas each bar represents the mean of all replicates. *, p < 0.05 compared to zero methylation stoichiometry, one-way ANOVA; #, p < 0.05 compared pairwise to all methyl-amino acid forms, ANOVA with Tukey’s post hoc test; n.s., not significant.