Induction of Alzheimer-specific tau epitope AT100 in apoptotic human fetal astrocytes

Hanna Ksiezak-Reding, Deke He, Wanda Gordon-Krajcer, Yvonne Kress, Sunhee Lee, Dennis W. Dickson

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

In Alzheimer's and other neurodegenerative diseases, hyperphosphorylated tau accumulates in affected neuronal and glial cells in the form of paired helical filaments (PHFs). This tau binds antibody AT100, which recognizes the double phosphorylation site (Thr212/Ser214) that is not present in normal biopsy tau. In primary cultures, highly enriched (>98%) in astrocytes of human fetal brain, three polypeptides of 52, 64, and 70 kD showed immunoreactivity with tau antibodies against non-phosphorylated epitopes, accounting for 88, 12, and <1%, respectively, of the total reactivity. All three polypeptides were phosphorylated at the PHF-1 epitope but not at the epitopes Tau-1, 12E8, AT8, and AT100. Treatment of cultures with okadaic acid resulted in apoptosis characterized by the blebbing of the plasma membrane, condensation of nuclear chromatin, and fragmentation of the nucleus. This treatment also resulted in a 3- to 5-fold increase in the content of both tau protein and phosphorylation. The increases were observed in all phosphorylation sites examined, and included the AT100 site. The AT100 site has been proposed to be generated by protein kinase B/Akt and Cdc2. Since okadaic acid can induce an AD-like hyperphosphorylated state of normal tau in primary cultures of human brain cells, a simple cellular model is available permitting study of self-aggregation of tau and phosphorylation events characteristic of neurodegeneration. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)236-252
Number of pages17
JournalCell motility and the cytoskeleton
Volume47
Issue number3
DOIs
Publication statusPublished - Nov 15 2000

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Keywords

  • Alzheimer's disease
  • Apoptosis
  • Okadaic acid
  • Primary cultures
  • Tau phosphorylation
  • Tau protein

ASJC Scopus subject areas

  • Structural Biology
  • Cell Biology

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