Phorbol ester enhances phosphorylated tau protein immunoreactivity in neuronal cultures

One of the hallmarks of Alzheimer's disease (AD) is neurofibrillary degeneration which results from the aggregation of phosphorylated tau proteins into paired helical filament (PHF) structures. AD2 is a new monoclonal antibody raised against PHF tau which detects neurofibrillary tangles in AD brain. In primary neuronal cultures, phorbol ester treatment induced a time- and dose-dependent increase in AD2 immunoreactivity quantified by laser confocal microscopy and immunoblottings. Alkaline phosphatase treatment reversed these immunocytochemical changes. These results suggest that the modifications of neuronal metabolism induced by phorbol ester including protein kinase C activation produce an increase in phosphorylated tau immunoreactivity.