title: A68: a major subunit of paired helical filaments and derivatized forms of normal Tau.
abstract: Putative Alzheimer disease (AD)-specific proteins (A68) were purified to homogeneity and shown to be major subunits of one form of paired helical filaments (PHFs). The amino acid sequence and immunological data indicate that the backbone of A68 is indistinguishable from that of the protein tau (tau), but A68 could be distinguished from normal human tau by the degree to which A68 was phosphorylated and by the specific residues in A68 that served as phosphate acceptors. The larger apparent relative molecular mass (Mr) of A68, compared to normal human tau, was attributed to abnormal phosphorylation of A68 because enzymatic dephosphorylation of A68 reduced its Mr to close to that of normal tau. Moreover, the LysSerProVal motif in normal human tau appeared to be an abnormal phosphorylation site in A68 because the Ser in this motif was a phosphate acceptor site in A68, but not in normal human tau. Thus, the major subunits of a class of PHFs are A68 proteins and the excessive or inappropriate phosphorylation of normal tau may change its apparent Mr, thus transforming tau into A68.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
authors.forename: V M
authors.initials: VM
authors.lastname: Lee
authors.forename: B J
authors.initials: BJ
authors.lastname: Balin
authors.forename: L
authors.initials: L
authors.lastname: Otvos
authors.forename: J Q
authors.initials: JQ
authors.lastname: Trojanowski
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010750:Phosphoproteins / Q000378:metabolism; D016875:tau Proteins
chemical_list: D000911:Antibodies, Monoclonal; D008869:Microtubule-Associated Proteins; D010750:Phosphoproteins; D016875:tau Proteins