Phosphorylated serine422 on tau proteins is a pathological epitope found in several diseases with neurofibrillary degeneration

Neuronal inclusions with bundles of abnormal filaments made of tau polymers are found in numerous diseases with neurofibrillary degeneration. Tau prot eins are the basic components of paired helical filaments (PHF) in Alzheime r's disease (AD), and are abnormally phosphorylated. A disease-specific pho sphorylation site at serine422 was demonstrated on PHF, but not on tau prot eins from biopsy-derived brain samples. In the present study, we report the characterization of a polyclonal antibody (988) against the serine422 phos phorylation site. By using biochemical and immunohistochemical methods, we confirmed that it is not found on tau proteins from biopsy- or autopsy-deri ved control samples, and we investigated the presence of this epitope on ta u proteins in several neurodegenerative disorders, including AD, Down syndr ome (DS), Guamanian amyotrophic lateral sclerosis/Parkinsonism-dementia com plex (ALS/PDC), corticobasal degeneration (CBD), progressive supranuclear p alsy (PSP), postencephalitic parkinsonism (PEP) and Pick's disease (PiD). B y Western blotting, antibody 988 labeled the characteristic tau triplet (ta u 55, 64, 69) in AD, DS, Guamanian ALS/PDC and PEP. PSP and CBD exhibited t heir typical tau doublet (tau 64, 69), whereas the doublet tau 55 and 64 wa s detected in PiD. In all of these neurodegenerative disorders, antibody 98 8 clearly labeled NFT and dystrophic neurites, as well as Pick bodies in Pi D cases, whereas no staining was observed in control cases. These data indi cate that phosphorylation of serine422 on tau proteins is a common feature among neurodegenerative disorders and is therefore not specific of AD. More over, phosphorylation of this epitope permits the distinction between norma l tau proteins and pathological tau proteins.