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 language | English (US) |
---|---|
Pages (from-to) | 621-630 |
Number of pages | 10 |
Journal | Journal of Alzheimer's Disease |
Volume | 19 |
Issue number | 2 |
DOIs | |
State | Published - 2010 |
Keywords
- Alzheimer's disease
- Amyloid-β
- Neurodegeneration
- Receptor binding
- TNF-α
- TNFRI
- TNFRII