Alzheimer's disease neurofibrillary tangles contain mitosis-specific phosphoepitopes

  • Kondratick C
  • Vandre D
  • 9

    Readers

    Mendeley users who have this article in their library.
  • 55

    Citations

    Citations of this article.

Abstract

Paired helical filaments (PHFs) are the major components of neurofibrillary lesions present in Alzheimer's disease (AD). PHFs are composed of the microtubule-associated protein (MAP) tau, which is abnormally phosphorylated in AD. Normal fetal tau is also phosphorylated and shares certain phosphoepitopes with PHF-tau. The abnormal phosphorylation of PHF-tau is considered to be involved in the formation of PHFs and subsequent degeneration of AD neurons. We have previously shown that other neuronal MAPs, such as MAP1B, contain mitosis-specific phosphoepitopes. In addition to mitotic cells, these epitopes are also expressed in fetal brain and PC12 cells during differentiation and neurite outgrowth. One hypothesis regarding the etiology of AD involves the reactivation of a fetal-like state and mitotic conditions in selected neurons. To determine if similar mitosis-associated phosphoepitopes appeared in AD, sections of hippocampal tissue were stained for immunoreactivity with antibodies recognizing both tau and mitotic phosphoepitopes. Both the MPM2 mitotic phosphoepitope antibody and the AT8 PHF-tau antibody stained neurofibrillary lesions and colocalized to pyramidal neurons in AD samples. In addition, PHFs isolated from an AD brain reacted with both antibodies. The MPM2 antibody specifically reacted with tau in the isolated PHF fraction but not normal adult tau. In addition, MPM2 failed to react with normal fetal or adult tau obtained from rat brains. The MPM2 antibody also recognized human MAP1B; however, MAP1B was not present in the PHF fraction. Our results indicate that MPM2 recognized a phosphoepitope present on PHF-tau. Because normal fetal or adult rat brain tau did not express the MPM2 epitope, it is likely that this phosphoepitope is specific for the disease state.

Author-supplied keywords

  • abnormal phosphorylation
  • alzheimer's disease
  • dependent kinase
  • fetal-type phosphorylation
  • glycogen-synthase kinase-3
  • microtubule-associated protein tau
  • microtubule-binding
  • mitotic spindle
  • monoclonal-antibody
  • neurofibrillary tangles
  • paired helical filaments
  • phosphoepitopes
  • protein-tau tau
  • rat-brain

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

  • PMID: 8931473
  • SCOPUS: 2-s2.0-0029824877
  • SGR: 0029824877
  • ISBN: 0022-3042
  • PUI: 26392511
  • ISSN: 0022-3042

Authors

  • C M Kondratick

  • D D Vandre

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free