Mitotic phosphoepitopes precede paired helical filaments in Alzheimer's disease

Inez Vincent, J. H. Zheng, D. W. Dickson, Y. Kress, P. Davies

Research output: Contribution to journalArticle

155 Scopus citations

Abstract

We have shown previously that the TG-3 and MPM-2 antibodies recognize phosphoepitopes common to mitosis and degenerating neurons of Alzheimer's disease(AD) brain. Here, we have evaluated their occurrence in human brain biopsy tissue, and confirm that they are absent in mature neurons of adult brain, but reappear during neurodegeneration in AD. The TG-3 epitope appears ahead of the MPM-2 epitope and is distributed throughout the neuronal soma. Tau is the major TG-3 antigen in AD brain. The initial localization of MPM-2 immunoreactivity in primary dendrites, it's robust occurrence in granulovacuolar bodies, and the increased immunoreactivity with 300-350-kDa proteins, suggest MAP1B as a candidate MPM-2 antigen in AD. Production of mitotic phosphepitopes in more than one type of human neurodegenerative lesion implicates mitotic kinases as common mediators of neuronal death. Because mitotic phosphoepitopes appear before paired helical filaments, it is suggested that mitotic kinase activation triggers neurofibrillary tangle formation. Future studies will need to focus on factors influencing mitotic kinase activity, a point with potential for early diagnosis and disease abrogation. Copyright (C) 1998 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)287-296
Number of pages10
JournalNeurobiology of aging
Volume19
Issue number4
DOIs
StatePublished - Jul 1 1998

Keywords

  • Alzheimer's disease
  • Cell cycle proteins
  • Cyclin B kinase
  • Granulovacuolar degeneration
  • MPM-2
  • Mitosis
  • Mitotic cdc2
  • Neurodegeneration
  • Neurofibrillary tangles
  • Neuronal death
  • Paired helical filaments
  • TG-3
  • Tau phosphorylation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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