Evidence for abnormal tau phosphorylation in early aggressive multiple sclerosis.

Although progression in multiple sclerosis is pathologically dominated by neurodegeneration, the underlying mechanism is unknown. Abnormal hyperphosphorylation of tau is implicated in the aetiopathogenesis of some common neurodegenerative disorders. We recently demonstrated the association of insoluble tau with established secondary progressive MS, raising the hypothesis that its accumulation is relevant to disease progression. In order to begin to determine the temporal emergence of abnormal tau with disease progression in MS, we examined tau phosphorylation in cerebral tissue from a rare case of early aggressive MS. We report tau hyperphosphorylation occurring in multiple cell types, with biochemical analysis confirming restriction to the soluble fraction. The absence of sarcosyl-insoluble tau fraction in early disease and its presence in secondary progression raises the possibility that insoluble tau accumulates with disease progression.