Altered Expression Levels of the Protein Phosphatase 2A ABαC Enzyme Are Associated with Alzheimer Disease Pathology

Estelle Sontag, Ampa Luangpirom, Christa Hladik, Ingrid Mudrak, Egon Ogris, Samuel Speciale, Charles L. White

Research output: Contribution to journalArticlepeer-review

182 Scopus citations

Abstract

The formation of amyloid-containing senile plaques and tau-rich neurofibrillary tangles are central events in Alzheimer disease (AD) pathogenesis. Significantly, ABαC, a major protein phosphatase 2A (PP2A) holoenzyme, specifically binds to and dephosphorylates tau. Deregulation of PP2A results in tau hyperphosphorylation in vivo. Here, we compared the expression levels and distribution of PP2A subunits in various brain regions from autopsy cases of AD and aged controls with or without histological evidence of age-related neurofibrillary degeneration. Immunoblotting analyses revealed that there was a significant reduction in the total amounts of ABαC in AD frontal and temporal cortices that matched the decrease in PP2A activity measured in the same brain homogenates. Immunohistochemical studies showed that neuronal ABαC expression levels were significantly and selectively decreased in AD-affected regions and in tangle-bearing neurons, but not in AD cerebellum and in non-AD dementias. Reduced neuronal ABαC immunoreactivity closely correlated with tangle load, but not plaque burden, suggesting that ABαC dysfunction contributes to AD tau pathology. Glial cells within senile plaques were also positive for ABαC. Increased glial PP2A immunoreactivity was observed in both AD and non-AD cases and may play a role in the brain's response to general inflammatory processes and amyloidogenesis.

Original languageEnglish (US)
Pages (from-to)287-301
Number of pages15
JournalJournal of neuropathology and experimental neurology
Volume63
Issue number4
DOIs
StatePublished - Apr 2004

Keywords

  • Alzheimer disease
  • Amyloid
  • Brain
  • Distribution
  • PP2A
  • Tau

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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