Department of Neurology, INSPE, Vita-Salute University and IRCCS-San Raffaele Hospital, Milan, Italy.
Nuclear Medicine Unit, IRCCS-San Raffaele Hospital, Milan, Italy.
Curr Alzheimer Res. 2019;16(7):587-595. doi: 10.2174/1567205016666190725150836.
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.
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.
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.
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.
针对阿尔茨海默病（AD）的新型疾病修饰疗法需要可靠的诊断标志物，以便在全球范围内正确招募患者。CSF 中的 AD 生物标志物，即淀粉样蛋白-β42（Aβ42）、总 tau（t-tau）和 tau 第 181 位苏氨酸磷酸化（p-tau181），在检测 AD 病理方面具有较好的诊断准确性，但它们在日常临床实践中的实际应用效果仍存在争议。因此，需要在更复杂的临床环境中进一步验证，即针对不同类型痴呆症的患者，以支持它们在全球范围内的未来应用。
我们在 526 名临床诊断为痴呆症的患者样本中测量了 CSF AD 生物标志物的浓度（277 名 AD 患者和 249 名其他类型痴呆症，OTD）。在 54 名临床诊断与 CSF 结果不匹配的患者的亚样本中还考虑了脑 FDG-PET。
p-tau181/Aβ42 比值高于 0.13 时，在区分 AD 与 OTD 方面具有最佳的诊断性能（准确度指数为 86%，敏感性为 74%，特异性为 81%）。在临床诊断与 CSF 结果不匹配的情况下，脑 FDG-PET 与 p-tau181/Aβ42 比值部分一致，从而提高了 CSF 的准确性。
单独的 p-tau181/Aβ42 比值可能可靠地检测出不同类型痴呆症患者异质样本中的 AD 病理。它可能是一种简单、具有成本效益且可重复的 AD 体内替代物，不仅可在日常临床实践中，也可在未来的实验性试验中在全球范围内采用，以避免招募到误诊的 AD 患者。
