Phosphate-dependent monoclonal antibodies to neurofilaments and Alzheimer neurofibrillary tangles recognize a synthetic phosphopeptide

Abstract

Five phosphate-dependent monoclonal antibodies to the neurofilament heavy polypeptide bound strongly to a phosphorylated synthetic peptide, which contains a single Lys-Ser-Pro sequence that occurs in human neurofilaments. Three of the antibodies label Alzheimer's disease neurofibrillary tangles and two do not, suggesting that in tangles an epitope similar to the peptide is available to some but not all of the antibodies. In addition, some antibodies were found to be more affected than others by enzymatic dephosphorylation of the antigen, but because all the antibodies bound the same synthetic phosphopeptide they do not bind to mutually exclusive phosphorylation sites. Instead the more phosphate-dependent antibodies might bind the phosphate group more directly, as suggested by their inhibition by inorganic phosphate and free phosphoserine.