Centre Mémoire Ressources Recherche Languedoc-Roussillon, CHU de Montpellier, hôpital Gui de Chauliac, Montpellier Cedex 5, France.
J Alzheimers Dis. 2013;34(1):297-305. doi: 10.3233/JAD-121549.
The French Alzheimer's Disease Plan aims, in an unprecedented national effort, to develop research, promote optimal diagnosis, and take better care of patients. In order to evaluate the clinical interest and use of cerebrospinal fluid (CSF) biomarkers, a data-sharing project, the PLM (Paris-North, Lille and Montpellier) study has emerged through collaboration between these memory centers, already involved in this field. The revised Alzheimer's disease (AD) diagnosis criteria include CSF biomarkers, but little is known about their use in routine clinical practice. To evaluate their interest and diagnostic accuracy in routine AD diagnosis, a cohort of 677 patients from Montpellier was first analyzed. The results were then validated through the analysis of a second cohort of 638 patients from Lille and Paris-Nord. Diagnoses of AD and other dementias were established by multidisciplinary expert teams, based on neuropsychological exams and structural brain imaging, blinded from CSF results. CSF amyloid-β, tau, and p-tau concentrations were measured for all patients. Receiver-operating characteristic curves were used to define cut-offs and evaluate the ability of each biomarker to discriminate AD from other diagnoses. We showed that p-tau outperformed other biomarkers for discriminating AD from non-AD patients and presents a clear clinical interest. The other biomarkers also showed relevant variations especially when the differential AD diagnoses were taken into account. Altogether we could demonstrate in both mono-centric and multi-centric cohorts from memory clinics the capacity of CSF biomarkers to discriminate AD from non-AD patients in clinical routine with a high sensitivity and specificity.
法国阿尔茨海默病计划旨在进行一次前所未有的国家努力，以发展研究、促进最佳诊断，并更好地照顾患者。为了评估脑脊液（CSF）生物标志物的临床意义和用途，一个数据共享项目——PLM（巴黎北部、里尔和蒙彼利埃）研究通过这些记忆中心之间的合作应运而生，这些中心已经参与了该领域的研究。经修订的阿尔茨海默病（AD）诊断标准纳入了 CSF 生物标志物，但对于其在常规临床实践中的应用知之甚少。为了评估 CSF 生物标志物在常规 AD 诊断中的应用价值和诊断准确性，我们首先对来自蒙彼利埃的 677 名患者进行了分析。然后，通过对来自里尔和巴黎北部的 638 名患者的分析对结果进行了验证。AD 和其他痴呆症的诊断由多学科专家团队根据神经心理学检查和结构脑成像确定，这些诊断与 CSF 结果无关。所有患者均进行了 CSF 淀粉样蛋白-β、tau 和 p-tau 浓度的检测。我们使用受试者工作特征曲线定义了临界值，并评估了每个生物标志物区分 AD 与其他诊断的能力。我们发现，p-tau 优于其他生物标志物，可用于区分 AD 患者与非 AD 患者，具有明显的临床意义。其他生物标志物在考虑到 AD 不同的鉴别诊断时也显示出了相关的变化。总之，我们在来自记忆诊所的单中心和多中心队列中都证明了 CSF 生物标志物在临床常规中区分 AD 患者与非 AD 患者的能力，具有较高的灵敏度和特异性。
