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- Title
Differential Activation of Tumor Necrosis Factor Receptors Distinguishes between Brains from Alzheimer's Disease and Non-Demented Patients.
- Authors
Xin Cheng; Libang Yang; Ping He; Rena Li; Yong Shen; Cheng-xin Gong
- 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.
- Subjects
TUMOR necrosis factors; BRAIN; ALZHEIMER'S disease; CYTOKINES; GLYCOPROTEINS
- Publication
Journal of Alzheimer's Disease, 2010, Vol 19, Issue 2, p621
- ISSN
1387-2877
- Publication type
Article
- DOI
10.3233/JAD-2010-1253