Phosphorylated serine 199 of microtubule-associated protein tau is a neuronal epitope abundantly expressed in youth and an early marker of tau pathology

Microtubule-associated protein tau is abnormally phosphorylated in many neurodegenerative disorders, and is the major component of neurofibrillary degeneration, a degenerating process with many biochemical phenotypes. The serine 199 (S199) residue of tau is phosphorylated at early and late stages of Alzheimer's disease (AD). We studied the immunohistochemical distribution of this phosphorylated epitope in AD and other neurodegenerative disorders, as well as in controls of different ages. The phosphorylated S199 (S199P) epitope was observed in tau lesions from numerous diseases with neurofibrillary degeneration. This epitope was found to be abundantly expressed in the hippocampus formation in childhood and in young adult brain samples, and more specifically in subsets of neurons vulnerable to neurodegeneration. Interestingly, our data suggests that S199P is particularly resistant to phosphatase activity occurring during post-mortem delays. We suggest a peculiar and important role of the S 199 residue as a qualitative indicator of the normal and pathological phosphorylation status of tau proteins.