Elevated CSF levels of TACE activity and soluble TNF receptors in subjects with mild cognitive impairment and patients with Alzheimer's disease

We recently reported that expression levels of tumor necrosis factor (TNF) receptors, TNFR1 and TNFR2, are significantly changed in the brains and cerebral spinal cerebral fluid (CSF) with Alzheimer's disease (AD). Moreo
We recently reported that expression levels of tumor necrosis factor (TNF) receptors, TNFR1 and TNFR2, are significantly changed in the brains and cerebral spinal cerebral fluid (CSF) with Alzheimer's disease (AD). Moreover, we also found that, in an Alzheimer's mouse model, genetic deletion of TNF receptor (TNFR1) reduces amyloid plaques and amyloid beta peptides (Abeta) production through beta-secretase (BACE1) regulation. TNF-alpha converting enzyme (TACE/ADAM-17) does not only cleave pro- TNF-alpha but also TNF receptors, however, whether the TACE activity was changed in the CSF was not clear. In this study, we examined TACE in the CSF in 32 AD patients and 27 age-matched healthy controls (HCs). Interestingly, we found that TACE activity was significantly elevated in the CSF from AD patients compared with HCs. Furthermore, we also assayed the CSF levels of TACE cleaved soluble forms of TNFR1 and TNFR2 in the same patients. We found that AD patients had higher levels of both TACE cleaved soluble TNFR1 (sTNFR1) and TNFR2 (sTNFR2) in the CSF compared with aged- and gender-matched healthy controls. Levels of sTNFR1 correlated strongly with the levels of sTNFR2 (rs = 0.567-0.663, p < 0.01). The levels of both sTNFR1 and sTNFR2 significantly correlated with the TACE activity (rs = 0.491-0.557, p < 0.05). To examine if changes in TACE activity and in levels of cleaved soluble TNFRs are an early event in the course of Alzheimer's disease, we measured these molecules in the CSF from 47 patients with mild cognitive impairment (MCI) which is considered as a preclinical stage of AD. Unexpectedly, we found significantly higher levels of TACE activity and soluble TNFR in the MCI group. These results suggest that TACE activity and soluble TNF receptors may be potential diagnostic candidate biomarkers in AD and MCI.
…show moreshow less

Download full text files

Export metadata

  • Export Bibtex
  • Export RIS

Additional Services

    Share in Twitter Search Google Scholar
Metadaten
Author:Hong Jiang, Harald Hampel, David Prvulovic, Anders Wallin, Kaj Blennow, Rena Li, Yong Shen
URN:urn:nbn:de:hebis:30:3-229537
DOI:http://dx.doi.org/doi:10.1186/1750-1326-6-69
ISSN:1750-1326
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=21978728
Parent Title (English):Molecular Neurodegeneration
Publisher:BioMed Central
Place of publication:London
Document Type:Article
Language:English
Date of Publication (online):2011/10/19
Date of first Publication:2011/10/06
Publishing Institution:Univ.-Bibliothek Frankfurt am Main
Release Date:2011/11/03
Tag:ADAM-17; Alzheimer's disease; biomarker; soluble tumor necrosis factor receptor; tumor necrosis factor converting enzyme
Volume:6
Issue:69
Pagenumber:8
First Page:1
Last Page:8
HeBIS PPN:280082878
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 2.0

$Rev: 11761 $