Phosphorylation differentiates tau-dependent neuronal toxicity and dysfunction.

The heterogeneous pathology of tauopathies and the differential susceptibility of different neuronal types to WT (wild-type) and mutant tau suggest that phosphorylation at particular sites rather than hyperphosphorylation mediates toxicity or dysfunction in a cell-type-specific manner. Pan-neuronal accumulation of tau in the Drosophila CNS (central nervous system) specifically affected the MBs (mushroom body neurons), consistent with neuronal type-specific effects. The MB aberrations depended, at least in part, on occupation of two novel phosphorylation sites: Ser(238) and Thr(245).