Department of Neuropsychiatry, Skaraborg Hospital, Falköping, Sweden.
J Alzheimers Dis. 2011;24(3):537-46. doi: 10.3233/JAD-2011-101878.
The cerebrospinal fluid (CSF) biomarkers amyloid-β (Aβ)(1-42), T-tau, and P-tau have good diagnostic accuracy for clinically diagnosed Alzheimer’s disease (AD). However, in multi-center studies, the predictive values of the CSF biomarkers have been lower, possibly due to differences in procedures for lumbar puncture and CSF handling and storage, and to differences in patient populations, clinical evaluations, and diagnostic procedures. Here we investigate the diagnostic accuracy of CSF biomarkers in a well defined homogeneous mono-center population. We also evaluate an extended panel of amyloid related biomarkers. Sixty consecutive patients admitted for cognitive impairment to a memory clinic were recruited. The participants included patients with AD or mild cognitive impairment (MCI) diagnosed with AD upon follow-up (n = 32), patients with stable MCI (n = 13), patients with other dementias diagnosed at primary evaluation or upon follow-up (n = 15), and healthy controls(n = 20). CSF was analyzed for Aβ(1-42), T-tau, and P-tau, and PA(X-38), Aβ(X-40), Aβ(X-42), sAβPPα, and sAβPPβ. In multivariate analysis, thecore biomarkers Aβ(1-42), T-tau, and P-tau demonstrated a high ability to diagnose AD versus the combined groups of controls and stable MCI, with an area under the receiver operating characteristic curve (AUROC) of 0.97 (95% CI 0.93–1.00, p < 0.0001). The additional biomarkers only marginally increased AUROC to 0.98 (95% CI 0.95–1.00, p < 0.0001), this increase mainly mediated by Aβ(X-42). In conclusion, CSF biomarkers Aβ(1-42), T-tau, and P-tau have very high diagnostic accuracy in a well defined cohort of untreated patients, demonstrating the excellent potency of CSF biomarkers to identify pathological processes in AD when astringent analytical protocol is used.
脑脊液（CSF）生物标志物淀粉样蛋白-β（Aβ）（1-42）、总 tau（T-tau）和磷酸化 tau（P-tau）对临床诊断的阿尔茨海默病（AD）具有良好的诊断准确性。然而，在多中心研究中，CSF 生物标志物的预测值较低，这可能是由于腰椎穿刺和 CSF 处理和储存程序的差异，以及患者人群、临床评估和诊断程序的差异。在这里，我们在一个定义明确的同质单中心人群中研究了 CSF 生物标志物的诊断准确性。我们还评估了一个扩展的淀粉样相关生物标志物面板。连续招募了 60 名因认知障碍而入住记忆诊所的患者。参与者包括 AD 或 AD 轻度认知障碍（MCI）患者（n = 32），经随访诊断为 AD；稳定 MCI 患者（n = 13）；在初次评估或随访时诊断为其他痴呆症的患者（n = 15）；和健康对照者（n = 20）。分析 CSF 中的 Aβ（1-42）、T-tau 和 P-tau，以及 PA（X-38）、Aβ（X-40）、Aβ（X-42）、sAβPPα 和 sAβPPβ。在多变量分析中，核心生物标志物 Aβ（1-42）、T-tau 和 P-tau 显示出很高的能力来诊断 AD 与对照和稳定 MCI 的合并组，其受试者工作特征曲线（ROC）下面积（AUROC）为 0.97（95%CI 0.93-1.00，p < 0.0001）。额外的生物标志物仅使 AUROC 略有增加至 0.98（95%CI 0.95-1.00，p < 0.0001），这主要是由 Aβ（X-42）介导的。总之，在定义明确的未经治疗患者队列中，CSF 生物标志物 Aβ（1-42）、T-tau 和 P-tau 具有非常高的诊断准确性，证明了当使用严格的分析方案时，CSF 生物标志物具有很高的识别 AD 中病理过程的潜力。
