Schuitemaker Alie, Dik Miranda G, Veerhuis Robert, Scheltens Philip, Schoonenboom Niki S M, Hack C Erik, Blankenstein Marinus A, Jonker Cees
Department of Neurology/Alzheimer Center, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
Neurobiol Aging. 2009 Nov;30(11):1885-9. doi: 10.1016/j.neurobiolaging.2008.01.014. Epub 2008 Apr 18.
The aim of this study was to demonstrate the involvement of the inflammatory proteins IL-6, ACT and CRP early in the pathology process of AD in patients with mild cognitive impairment (MCI) and AD.
IL-6, ACT, CRP, Abeta42, phospho-tau (p-tau) and total tau concentrations in serum and CSF of 145 patients with probable AD and 67 patients with MCI were measured by sandwich ELISA. MCI patients were characterized as high- respectively low-risk MCI according to their Abeta42/tau risk profile.
CSF and serum CRP levels were significantly higher in MCI compared to AD patients after adjustment for age, ApoE epsilon4 genotype and cardiovascular diseases (p<0.01). This difference remained present in patients with a low-risk biomarker profile for AD after adjustment for abovementioned covariates. CSF IL-6 levels were also significantly higher in MCI patients with a low-risk CSF profile.
These findings suggest that inflammatory processes might be involved in early stages of AD, even before Abeta and tau changes are present in CSF of MCI patients.
本研究旨在证明炎症蛋白白细胞介素-6（IL-6）、活化素A（ACT）和C反应蛋白（CRP）在轻度认知障碍（MCI）和阿尔茨海默病（AD）患者AD病理过程早期的作用。
采用夹心酶联免疫吸附测定法（ELISA）检测145例可能患有AD的患者和67例MCI患者血清及脑脊液中IL-6、ACT、CRP、β淀粉样蛋白42（Aβ42）、磷酸化tau蛋白（p-tau）和总tau蛋白的浓度。根据Aβ42/tau风险谱，MCI患者被分为高风险和低风险MCI。
在调整年龄、载脂蛋白Eε4（ApoE ε4）基因型和心血管疾病后，MCI患者脑脊液和血清中的CRP水平显著高于AD患者（p<0.01）。在调整上述协变量后，AD低风险生物标志物谱的患者中这种差异仍然存在。脑脊液IL-6水平在脑脊液低风险谱的MCI患者中也显著更高。
这些发现表明，炎症过程可能参与AD的早期阶段，甚至在MCI患者脑脊液中出现Aβ和tau变化之前。
