Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology

Proc Natl Acad Sci U S A. 1986 Jul;83(13):4913-7. doi: 10.1073/pnas.83.13.4913.

Abstract

A monoclonal antibody to the microtubule-associated protein tau (tau) labeled some neurofibrillary tangles and plaque neurites, the two major locations of paired-helical filaments (PHF), in Alzheimer disease brain. The antibody also labeled isolated PHF that had been repeatedly washed with NaDodSO4. Dephosphorylation of the tissue sections with alkaline phosphatase prior to immunolabeling dramatically increased the number of tangles and plaques recognized by the antibody. The plaque core amyloid was not stained in either dephosphorylated or nondephosphorylated tissue sections. On immunoblots PHF polypeptides were labeled readily only when dephosphorylated. In contrast, a commercially available monoclonal antibody to a phosphorylated epitope of neurofilaments that labeled the tangles and the plaque neurites in tissue did not label any PHF polypeptides on immunoblots. The PHF polypeptides, labeled with the monoclonal antibody to tau, electrophoresed with those polypeptides recognized by antibodies to isolated PHF. The antibody to tau-labeled microtubules from normal human brains assembled in vitro but identically treated Alzheimer brain preparations had to be dephosphorylated to be completely recognized by this antibody. These findings suggest that tau in Alzheimer brain is an abnormally phosphorylated protein component of PHF.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Antibodies, Monoclonal
  • Cytoskeleton / ultrastructure
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Humans
  • Immunologic Techniques
  • Microtubule-Associated Proteins / immunology
  • Microtubule-Associated Proteins / metabolism*
  • Phosphoproteins / immunology
  • Phosphoproteins / metabolism
  • Phosphorylation
  • tau Proteins

Substances

  • Antibodies, Monoclonal
  • Microtubule-Associated Proteins
  • Phosphoproteins
  • tau Proteins