BACKGROUND The incoming disease-modifying therapies against Alzheimer's disease (AD) require reliable diagnostic markers to correctly enroll patients all over the world. CSF AD biomarkers, namely amyloid-β 42 (Aβ42), total tau (t-tau), and tau phosphorylated at threonine 181 (p-tau181), showed good diagnostic accuracy in detecting AD pathology, but their real usefulness in daily clinical practice is still a matter of debate. Therefore, further validation in complex clinical settings, that is patients with different types of dementia, is needed to uphold their future worldwide adoption. METHODS We measured CSF AD biomarkers' concentrations in a sample of 526 patients with a clinical diagnosis of dementia (277 with AD and 249 with Other Type of Dementia, OTD). Brain FDG-PET was also considered in a subsample of 54 patients with a mismatch between the clinical diagnosis and the CSF findings. RESULTS A p-tau181/Aβ42 ratio higher than 0.13 showed the best diagnostic performance in differentiating AD from OTD (86% accuracy index, 74% sensitivity, 81% specificity). In cases with a mismatch between clinical diagnosis and CSF findings, brain FDG-PET partially agreed with the p-tau181/Aβ42 ratio, thus determining an increase in CSF accuracy. CONCLUSION The p-tau181/Aβ42 ratio alone might reliably detect AD pathology in heterogeneous samples of patients suffering from different types of dementia. It might constitute a simple, cost-effective and reproducible in vivo proxy of AD suitable to be adopted worldwide not only in daily clinical practice but also in future experimental trials, to avoid the enrolment of misdiagnosed AD patients.

中文翻译：

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CSF p-tau181 /Aβ42比值在阿尔茨海默氏痴呆的鉴别诊断中提供了“体内”的良好准确性。

背景技术针对阿尔茨海默氏病（AD）的即将到来的疾病改良疗法需要可靠的诊断标记物来正确招募全世界的患者。CSF AD生物标志物，即淀粉样蛋白-β42（Aβ42），总tau（t-tau）和在苏氨酸181磷酸化的tau（p-tau181），在检测AD病理学方面显示出良好的诊断准确性，但在日常临床实践中真正有用仍然是一个辩论的问题。因此，需要在复杂的临床环境中（即患有不同类型痴呆症的患者）进行进一步验证，以维护他们未来在全球范围内的采用。方法我们在526例患有痴呆临床诊断的患者（277例AD和249例其他类型的痴呆，OTD）中测量了CSF AD生物标志物的浓度。54例患者的子样本中还考虑了脑FDG-PET，其临床诊断与CSF结果不匹配。结果高于0.13的p-tau181 /Aβ42比值显示出将AD与OTD区分的最佳诊断性能（准确度指标为86％，灵敏度为74％，特异性为81％）。如果临床诊断与脑脊液检查结果不匹配，则脑FDG-PET部分符合p-tau181 /Aβ42的比率，从而确定脑脊液准确性的提高。结论单独的p-tau181 /Aβ42比值可以可靠地检测患有不同类型痴呆的异质患者样本中的AD病理。它可能构成了一种简单，经济高效且可重现的AD体内替代药物，不仅可以在全世界的日常临床实践中使用，而且可以在以后的实验中广泛采用，