Background: Amyloid pathology, which is one of the characteristics of Alzheimer's disease (AD), results from altered metabolism of the beta-amyloid peptide (Aβ) in terms of synthesis, clearance or aggregation. A decrease in cerebrospinal fluid (CSF) level Aβ1-42 is evident in AD, and the CSF ratio Aβ40 /Aβ40 has recently been identified as one of the most reliable diagnostic biomarkers of amyloid pathology. Variations in inter-individual levels of Aβ1-40 in the CSF have been observed in the past, but their origins remain unclear. In addition, the variation of Aβ40 in the context of AD studied in several studies has yielded conflicting results. Methods: Here, we analyzed the levels of Aβ1-40 using multicenter data obtained on 2466 samples from six different cohorts in which CSF was collected under standardized protocols, centrifugation and storage conditions. Tau and p-tau(181) concentrations were measured using commercially available in vitro diagnostic immunoassays. Concentrations of CSF Aβ1-42 and Aβ1-40 were measured by ELISA, xMAP technology, chemiluminescence immunoassay (CLIA) and mass spectrometry. Statistical analyses were calculated for parametric and non-parametric comparisons, linear regression, correlation and odds ratios. The statistical tests were adjusted for the effects of covariates (age, in particular). Results: Regardless of the analysis method used and the cohorts, a slight but significant age-independent increase in the levels of Aβ40 in CSF was observed in AD. We also found a strong positive correlation between the levels of Aβ40 and p-tau(181) in CSF, particularly in control patients. Conclusions: These results indicate that an increase in the baseline level of amyloid peptides, which are associated with an increase in p-tau(181), may be a biological characteristic of AD. This confirms the potential therapeutic value of lowering the baseline levels of Aβ40 which, being elevated, can be considered a risk factor for the disease.

中文翻译：

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脑脊液中的β1-40肽在阿尔茨海默氏病中增加，并且与对照组的磷酸化tau高度相关

背景：淀粉样变性是阿尔茨海默氏病（AD）的特征之一，是由于β淀粉样肽（Aβ）的代谢在合成，清除或聚集方面发生改变而引起的。在AD中，脑脊液（ASF1-42）水平明显降低，并且最近已将CSF比率Aβ40/Aβ40确定为淀粉样蛋白病理学的最可靠的诊断生物标志之一。过去已经观察到脑脊液中个体间Aβ1-40水平的变化，但其起源尚不清楚。另外，在若干研究中研究的AD中Aβ40的变化产生了矛盾的结果。方法：在这里，我们使用从六个不同队列中的2466个样本中获得的多中心数据分析了Aβ1-40的水平，这些样本是在标准化协议下收集脑脊液的，离心和储存条件。Tau和p-tau（181）的浓度使用市售的体外诊断性免疫测定法进行测量。通过ELISA，xMAP技术，化学发光免疫分析（CLIA）和质谱法测量CSFAβ1-42和Aβ1-40的浓度。计算统计分析以进行参数和非参数比较，线性回归，相关性和优势比。调整统计检验的协变量效应（尤其是年龄）。结果：无论采用何种分析方法和队列，在AD中均观察到CSF中Aβ40水平的轻微但显着的年龄依赖性升高。我们还发现脑脊液中Aβ40和p-tau（181）的水平之间存在很强的正相关，特别是在对照患者中。结论：这些结果表明，与p-tau（181）增加相关的淀粉样蛋白肽基线水平的增加可能是AD的生物学特征。这证实了降低Aβ40的基线水平的潜在治疗价值，该水平升高被认为是该疾病的危险因素。