Figure 3. Critical role for tau in Aβ toxicity.

That tau is critical for Aβ-mediated toxicity, has been shown in primary neuronal cultures: wild-type (wt) neurons (A) degenerated when incubated with Aβ42, as did tau-transfected neurons (C). Primary neurons derived from tau knockout (KO) mice, however, were resistant to the toxic effects of Aβ (B). This has been translated in vivo. Most, if not all, APP mutant strains with a robust Aβ plaque pathology are characterized by premature death of unknown cause. This includes APP mutant J20 mice (D). By crossing these on to a hetero- or homo-zygous tau knockout background many clinical features could be ameliorated (E).