Elevated Plasma Levels of Soluble TNFRs and TACE Activity in Alzheimer's Disease Patients of Northern Han Chinese Descent

Background: We recently reported elevated cerebrospinal fluid (CSF) levels of soluble tumor necrosis factor (TNF) receptors and TNF-alpha converting enzyme (TACE) activity in subjects with Alzheimer's disease (AD) in a Caucasian population. The TNF receptor-mediated signaling pathway contributes to the production of A beta and the subsequent cytotoxicity that is observed in AD brains. However, whether the plasma levels of soluble TNF receptors (sTNFRs) are changed is still unclear in AD patients of Han descent. Methods: In the present study, we analyzed the plasma sTNFR levels using commercially available immunoassay kits in 76 AD patients and 40 age-and sex-matched control subjects of Northern Han Chinese descent. Furthermore, the TACE activity was measured using a solution-based assay containing a fluorescently labeled TACE substrate. Results: AD patients exhibited higher levels of both sTNFR and TACE activity in their plasma compared with age-and sex-matched control subjects. The levels of sTNFR1 strongly correlated with the levels of sTNFR2 (r(s) = 0.526, P<0.001). In addition, the levels of sTNFR1 were significantly correlated with TACE activity (r(s) = 0.308, P<0.01). Conclusion: These results suggest that sTNFRs and TACE activity might serve as potential peripheral diagnostic candidate biomarkers in AD.