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Fig. 1 | Acta Neuropathologica Communications

Fig. 1

From: Tau Ser208 phosphorylation promotes aggregation and reveals neuropathologic diversity in Alzheimer’s disease and other tauopathies

Fig. 1

Triple phosphomimetic S202E/T205E/S208E promotes aggregation of WT tau. a Schematic of 2N4R human tau protein depicting the major domains and the expanded 199–208 amino acid region within the proline-rich domain. Ser202, Thr205, and Ser208 were mutated to Glu residues to model site-specific tau phosphorylation. b HEK293T cells were transfected to express 2N4R human WT tau (b), P301L tau mutant (c), or the indicated tau phosphomimetics (d-g) and were biochemically assessed for tau aggregation with or without the addition of K18 seeds as described in “Materials and Methods.” S = supernatant fraction, P = pellet fractions. Immunoblots were probed with total tau antibody 3026. c As a positive control for seeding with K18 seeds the tau P301L mutant was used. Similar aggregation and seeding studies were performed with the single phosphomimetic S208E (d), the double phosphomimetic S202E/T205E (e), and the triple phosphomimetic S202E/T205E/S208E (f). g Triple phosphomimetic S202E/T205E/S208E in the context of the P301L mutation was also assessed. The relative molecular masses of protein markers are indicated on the left. h Quantification of percent tau aggregation was determined as described in “Materials and Methods.” One-way ANOVA with Dunnett’s Test was performed with N = 6 for WT tau and N = 3 for each tau mutant. **** is p < 0.0001, *** is p < 0.001, * is p < 0.05 and ns = not statistically significant. Error bars show standard error of the mean

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