TAU ANTIGENIC CHANGES INDUCED BY GLUTAMAT E ON PRIMARY NEURONAL CULTURES - IMMUNOCYTOCHEMISTRY STUDIES

Degenerating neurons in Alzheimer's disease are characterized by the p resence of neurofibrillary tangles constitued by paired helical filame nts (PHF). Abnormally phosphorylated Tau protein, a microtubule associ ated protein is one of the major component of PHF. Abnormal phosphoryl ation seems to be located in the C-terminal domain but also in the N-t erminal region of Tau proteins. Previous studies demonstrated that cal cium-mediated glutamate toxicity produces a dose-dependent increase of Tau immunolabellings in neuronal cultures. Biochemical results reveal ed that these changes could be associated with abnormal Tau migrations on immunoblots. Using three anti-Tau antibodies the present study sho ws that glutamate toxicity induces in neuronal cultures, Tau modificat ions localized in the N- and C-terminal domains of the protein. These findings suggest the possibility that glutamate toxicity can induce Ta u antigenic changes involving probably the whole molecule.