Figure 2
From: Alzheimer brain-derived tau oligomers propagate pathology from endogenous tau
Brain-derived tau oligomers propagate in vitro.
(a) Monomeric recombinant full-length tau was seeded (70/1 wt/wt) by either brain-derived oligomers (striped bars) or tau oligomers prepared in vitro (black). AD brain-derived tau oligomers induced aggregation of recombinant tau monomer as quantified by ELISA using T22; brain derived tau oligomers are more potent seeds than the oligomers prepared in vitro, after 24 hrs incubation monomeric tau fully assembled into oligomers. (b) Tau oligomers prepared using brain-derived oligomer seeds (24 hrs) were characterized by SEC; it is clear that at this time point the solution contains homogeneous population of tau oligomers (dimer/trimer). This was confirmed by AFM (inset). Scale bar, 10 nm. (c) Circular dichroism (CD) spectroscopy of tau oligomers formed after 24 hrs incubation (0.2 mg/ml in PBS) demonstrates that tau oligomers are β-sheet rich with minimum ellipticity (~213 nm). (d) Tau oligomers prepared using brain-derived oligomer seeds were more toxic to cells (at a much lower concentration) than oligomers prepared using seeds prepared from recombinant tau in vitro. Preincubation of tau oligomers with T22 (1:4 (mol/mol) for 1 hr) eliminated their toxicity as assessed by dye reduction assay using neuroblastoma cells. (** P <0.001; * P <0.01, two-way ANOVA).
