It has been suggested that Aβ accumulation could increase phosphorylation and accumulation of tau24,25. To assess the potential causal relationship between increased Aβ production and increased p-tau levels, we treated apoE4/4 neurons with an inhibitor of β-secretase (OM99-2) or γ-secretase (compound E) for 1 week10. Aβ40 and Aβ42 levels in the culture medium decreased by 60–75% (OM99-2) and >95% (compound E) (Fig. 2a,b). Strikingly, despite these drastic reductions of Aβ levels, p-tau levels were unaffected in apoE4/4 neurons, as shown by western blot analysis with monoclonal antibodies AT8 and AT180 (Fig. 2c–e).
