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

Authors: Cheng, Xin  Yang, Libang  He, Ping  Li, Rena  Shen, Yong 
Citation: Cheng X, etal., J Alzheimers Dis. 2010;19(2):621-30. doi: 10.3233/JAD-2010-1253.
Pubmed: (View Article at PubMed) PMID:20110607
DOI: Full-text: DOI:10.3233/JAD-2010-1253

We reported that tumor necrosis factor receptor I (TNFRI) is required for neuronal death induced by amyloid-beta 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 125I-TNF-alpha binding technique, we found that, in AD brains, 125I-TNF-alpha 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.

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CRRD Object Information
CRRD ID: 13825249
Created: 2018-12-03
Species: All species
Last Modified: 2018-12-03
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.