Direct interaction of soluble human recombinant tau protein with Aβ 1–42 results in tau aggregation and hyperphosphorylation by tau protein kinase II

Abstract

We report here that aggregated β-amyloid (Aβ) 1–42 promotes tau aggregation in vitro in a dose-dependent manner. When Aβ-mediated aggregated tau was used as a substrate for tau protein kinase II (TPK II), an 8-fold increase in the rate of TPK II-mediated tau phosphorylation was observed. The extent of TPK II-dependent tau phosphorylation increased as a function of time and Aβ 1–42 concentration, and hyperphosphorylated tau was found to be decorated with an Alzheimer’s disease-related phosphoepitope (P-Thr-231). In HEK 293 cells co-expressing CT-100 amyloid precursor protein and tau, the release of Aβ 1–42 from these cells was impaired. Taken together, these in vitro results suggest that Aβ 1–42 promotes both tau aggregation and hyperphosphorylation.