Characterization of mAb AP422, a novel phosphorylation-dependent monoclonal antibody against tau protein.

A monoclonal antibody (AP422) specific for phosphoserine 422 in microtubule-associated protein tau has been produced. It strongly labels paired helical filament (PHF) tau from Alzheimer's disease brain in a phosphorylation-dependent manner. By contrast, AP422 only labels a small fraction of fetal tau and a very small fraction of tau from adult brain. The amount of tau phosphorylated at Ser-422 in normal brain is minor relative to that phosphorylated at sites recognized by other phosphorylation-dependent anti-tau antibodies of known epitope. It follows that AP422 is the most specific anti-tau antibody available for detecting the neurofibrillary lesions of Alzheimer's disease. We also show that Ser-422 in tau is a good in vitro substrate for mitogen-activated protein kinase, but not for glycogen synthase kinase-3 or neuronal cdc2-like kinase.