Department of Clinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen, Denmark.
J Alzheimers Dis. 2013;37(2):379-87. doi: 10.3233/JAD-122410.
A relation between amyloid-β peptide (Aβ) accumulation and neprilysin (NEP), an Aβ degrading enzyme, has been proposed but studies of NEP and the levels of the pathological hallmarks of Alzheimer's disease (AD), Aβ and tau, in cerebrospinal fluid (CSF) are scarce. In this study, we measured the level and enzyme activity of NEP in serum and CSF, using a sandwich enzyme-linked immunosorbent assay and a fluorescence resonance energy transfer assay, respectively, in patients with AD, frontotemporal dementia (FTD), Creutzfeldt-Jakob disease (CJD), and depression. Results were correlated with the levels of CSF AD biomarkers Aβ42, hyperphosphorylated tau (p-tau), and total tau (t-tau). In serum, we found no differences in NEP-like activity or concentration between the groups and there were no correlations between NEP and AD biomarkers. In CSF, no influence of age or gender on NEP levels or enzyme activity was seen. However, NEP concentration was lower and the specific activity was higher in FTD compared to AD. Aβ42 levels in CSF did not correlate with NEP concentration or activity in the AD, CJD, or depression groups, but NEP-like activity and Aβ42 levels correlated significantly in the FTD group. In AD and depression, the NEP-like activity in CSF correlated with levels of p-tau, and, in the AD group, it also was correlated with t-tau levels. Our results suggest that the relation between the specific activity of NEP and t-tau and p-tau is a characteristic trait of AD. The correlation between NEP concentration and Aβ42 in FTD is unexpected and warrants further investigation.
淀粉样β肽（Aβ）积累与神经肽酶（NEP）之间的关系已被提出，但对 NEP 以及阿尔茨海默病（AD）的病理标志物 Aβ和tau在脑脊液（CSF）中的水平的研究还很少。在这项研究中，我们使用夹心酶联免疫吸附测定法和荧光共振能量转移测定法分别测量了 AD、额颞叶痴呆（FTD）、克雅氏病（CJD）和抑郁症患者血清和 CSF 中 NEP 的水平和酶活性，并将结果与 CSF AD 生物标志物 Aβ42、磷酸化 tau（p-tau）和总 tau（t-tau）的水平相关联。在血清中，我们没有发现各组之间 NEP 样活性或浓度存在差异，并且 NEP 与 AD 生物标志物之间没有相关性。在 CSF 中，年龄或性别对 NEP 水平或酶活性没有影响。然而，与 AD 相比，FTD 中 NEP 浓度较低，特异性活性较高。AD、CJD 或抑郁症组 CSF 中的 Aβ42 水平与 NEP 浓度或活性均无相关性，但 FTD 组中 NEP 样活性与 Aβ42 水平显著相关。在 AD 和抑郁症中，CSF 中的 NEP 样活性与 p-tau 水平相关，并且在 AD 组中，它也与 t-tau 水平相关。我们的研究结果表明，NEP 特异性活性与 t-tau 和 p-tau 的关系是 AD 的特征性特征。FTD 中 NEP 浓度与 Aβ42 的相关性出乎意料，值得进一步研究。
