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PMID: 20110607 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Journal of Alzheimer's disease : JAD ·Vol. 19 ·No. 2 ·2010-00-00 ·Pages 621-30

Cheng X, Yang L, He P, Li R, Shen Y

Abstract

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.

MeSH Terms
Aged, 80 and over Alzheimer Disease/pathology,physiopathology Brain/drug effects,metabolism Dose-Response Relationship, Drug Enzyme-Linked Immunosorbent Assay/methods Female Gene Expression Regulation/physiology Glial Fibrillary Acidic Protein/metabolism Humans Iodine Isotopes/pharmacokinetics Male Phosphopyruvate Hydratase/metabolism Postmortem Changes RNA, Messenger/metabolism Radioligand Assay/methods Receptors, Tumor Necrosis Factor, Type I/genetics,metabolism Receptors, Tumor Necrosis Factor, Type II/genetics,metabolism Tumor Necrosis Factor-alpha/pharmacokinetics
Chemicals
Glial Fibrillary Acidic Protein Iodine Isotopes RNA, Messenger Receptors, Tumor Necrosis Factor, Type I Receptors, Tumor Necrosis Factor, Type II Tumor Necrosis Factor-alpha Phosphopyruvate Hydratase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Cheng Xin
Haldeman Laboratory of Molecular and Cellular Neurobiology, Sun Health Research Institute, Sun City, AZ, USA.
Yang Libang
He Ping
Li Rena
Shen Yong
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Article Info
Journal
Journal of Alzheimer's disease : JAD
Abbr.
J Alzheimers Dis
ISSN
1875-8908
DOI
10.3233/JAD-2010-1253
Published
2010-00-00
Pages
621-30
Language
English
Region
Netherlands
NLM ID
9814863
PMCID
PMC3746510
Subset
IM
Grants
NIA NIH HHS · R01 AG025888 · United States
NIA NIH HHS · R01 AG032441 · United States
NIA NIH HHS · R01AG025888 · United States
External Links
PubMed source DOI: 10.3233/JAD-2010-1253 PMC Full Text View journal details
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