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

Abstract
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.

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