p38 Kinase is activated in the Alzheimer's disease brain

Kenneth Hensley, Robert A. Floyd, Nai Ying Zheng, Raha Nael, Kent A. Robinson, Xuan Nguyen, Quentin N. Pye, Charles A. Stewart, James Geddes, William R. Markesbery, Ela Patel, Gail V.W. Johnson, Guoying Bing

Research output: Contribution to journalArticlepeer-review

331 Scopus citations

Abstract

The p38 mitogen-activated protein kinase is a stress-activated enzyme responsible for transducing inflammatory signals and initiating apoptosis. In the Alzheimer's disease (AD) brain, increased levels of phosphorylated (active) p38 were detected relative to age-matched normal brain. Intense phospho-p38 immunoreactivity was associated with neuritic plaques, neuropil threads, and neurofibrillary tangle-bearing neurons. The antibody against phosphorylated p38 recognized many of the same structures as an antibody against aberrantly phosphorylated, paired helical filament (PHF) tau, although PHF-positive tau did not cross-react with the phospho-p38 antibody. These findings suggest a neuroinflammatory mechanism in the AD brain, in which aberrant protein phosphorylation affects signal transduction elements, including the p38 kinase cascade, as well as cytoskeletal components.

Original languageEnglish
Pages (from-to)2053-2058
Number of pages6
JournalJournal of Neurochemistry
Volume72
Issue number5
DOIs
StatePublished - 1999

Keywords

  • Alzheimer's disease
  • Dementia
  • Inflammation
  • Tau
  • p38 kinase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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