One of the hallmarks of Alzheimer's disease (AD) is neurofibrillary de
generation which results from the aggregation of phosphorylated tau pr
oteins into paired helical filament (PHF) structures. AD(2) is a new m
onoclonal antibody raised against PHF tau which detects neurofibrillar
y tangles in AD brain. In primary neuronal cultures, phorbol ester tre
atment induced a time- and dose-dependent increase in AD(2) immunoreac
tivity quantified by laser confocal microscopy and immunoblottings. Al
kaline 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.