Affiliations: [a] Haldeman Laboratory of Molecular and Cellular Neurobiology, Sun Health Research Institute, Sun City, AZ, USA | [b] Department of Neurology and Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, China | [c] Laboratory of Molecular Endocrinology, Sun Health Research Institute, Sun City, AZ, USA | [d] Present address: Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA
Correspondence:
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Corresponding author: Yong Shen, Sun Health Research Institute, 10515 W. Santa Fe Drive, Sun City, AZ 85351, USA. Tel.: +1 623 876 5456; Fax: +1 623 876 6688; E-mail: yong.shen@bannerhealth.com.
Note: [1] These authors contributed equally to this study.
Note: [] Communicated by 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 125I-TNF-α binding technique, we found that, in AD brains, 125I-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.
