Differential activation of tumor necrosis factor receptors distinguishes between brains from Alzheimer's disease and non-demented patients

Xin Cheng, Libang Yang, Ping He, Rena Li, Yong Shen

Research output: Contribution to journalArticle

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Abstract

We reported that tumor necrosis factor receptor I (TNFRI) is required for neuronal death induced by amyloid-β protein in the Alzheimer's disease (AD) brain. However, whether TNF receptor subtypes are expressed and activated differentially in AD brains compared to non-demented brains remains unclear. Our studies on Western blot and ELISA measurements demonstrated that TNFRI levels are increased whereas TNFRII levels are decreased in AD brains compared to non-demented brains (p< 0.05). Immunohistochemical results demonstrated that both TNFRI and TNFRII are expressed in neurons in AD and non-demented brains. However, in situ hybridization studies showed little change in the mRNA levels of either type of TNF receptor in the neurons of AD brains compared to non-demented brains. To examine whether different levels of TNF receptors in AD brains are correlated with the alteration of functional binding of TNF receptors, by using ^{125}I-TNF-α binding technique, we found that, in AD brains, ^{125}I-TNF-α binding affinity to TNFRI is increased, whereas binding affinity to TNFRII is decreased (p< 0.01). These studies reveal a novel observation of abnormal TNF receptor activation in AD brains. Differential TNF receptor protein levels and binding affinities suggest distinct pathogenic mechanisms of neurodegeneration in the AD brain.

Original languageEnglish (US)
Pages (from-to)621-630
Number of pages10
JournalJournal of Alzheimer's Disease
Volume19
Issue number2
DOIs
StatePublished - 2010

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Keywords

  • Alzheimer's disease
  • Amyloid-β
  • Neurodegeneration
  • Receptor binding
  • TNF-α
  • TNFRI
  • TNFRII

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