Immunocytochemistry of tau phosphoserine 413 and tau protein kinase I in Alzheimer pathology

One unique phosphorylation site consistently found in paired helical filament tau, serine 413, is modified by tan protein kinase I/glycogen synthase kinase-3 beta but no other known tau kinase. Here we present immunocytochemistry from Alzheimer's disease brains showing that focal subpopulations of hippocampal CAI pyramidal neurons and neuritic plaques are strongly reactive for tau protein kinase I/gIycogen synthase kinase-3 beta and tau phosphoserine 413 in early stages of pathology. Colocalization of these epitopes suggests that tau protein kinase I/glycogen synthase kinase-3 beta abnormally phosphorylates tau and is in a position to disrupt neuronal metabolism in anatomical areas vulnerable to Alzheimer's disease.