Extended Data Fig. 3: Hyperphosphorylation is closely associated with tau seeding.
From: Tau molecular diversity contributes to clinical heterogeneity in Alzheimer’s disease
Brain extracts from the 32 AD subject were quantified for two epitopes of tau using alphaLISA (AT8 (a) and PHF6 (b)). Prior to this assay, samples were normalized for total protein amount as obtained using a BCA assay. Background Corrected Relative Light Unit (RLU) are plotted here. The color gradient scale bar relates to seeding quantities obtained in Fig. 2b. Both phospho-epitopes show a positive statistically significant association with tau seeding using a two-tailed Spearman’s rank non parametric correlation. SEC fractions from 9 AD brain extracts grouped into high seeders (red, n = 3), moderate seeders (green, n = 3) and low seeders (blue, n = 3) were tested for the presence of epitopes of tau hyperphosphorylation by alphaLISA (AT8 (d) and PHF6 (c)). Error bars represent the standard deviation to the mean. Showing the enriched presence of these epitopes in HMW fractions, especially in high and moderate seeders. e, HMW tau species quantified from the SDD-AGE (bin1-6, see Fig. 3b) were correlated with oligomeric tau levels from the alphaLISA showing a significant two-tailed Spearman’s rank nonparametric correlation. The r coefficient and p value are indicated on the plot. n = 14 individual subjects.