Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway.
Centre for Organelle Research, University of Stavanger, Stavanger, Norway.
Eur J Neurol. 2020 Jan;27(1):43-50. doi: 10.1111/ene.14032. Epub 2019 Jul 24.
Parkinson's disease (PD), dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are three of the most common neurodegenerative disorders. Up to 20% of these patients have the wrong diagnosis, due to overlapping symptoms and shared pathologies. A cerebrospinal fluid (CSF) biomarker panel for AD is making its way into the clinic, but an equivalent panel for PD and DLB and for improved differential diagnoses is still lacking. Using well-defined, community-based cohorts and validated analytical methods, the diagnostic value of CSF total-α-synuclein (t-α-syn) alone and in combination with total tau (t-tau) in newly diagnosed patients with PD, DLB and AD was determined.
Cerebrospinal fluid concentrations of t-α-syn were assessed using our validated in-house enzyme-linked immunosorbent assay in 78 PD patients, 20 AD patients, 19 DLB patients and 32 controls. t-tau was measured using a commercial assay. Diagnostic performance was assessed by receiver operating characteristic curve analysis.
Compared to controls (mean 517 pg/ml), significantly lower levels of CSF t-α-syn in patients with PD (434 pg/ml, 16% reduction, P = 0.036), DLB (398 pg/ml, 23% reduction, P = 0.009) and AD (383 pg/ml, 26% reduction, P = 0.014) were found. t-α-syn levels did not differ significantly between PD, DLB and AD. The t-tau/t-α-syn ratio showed an improved performance compared to the single markers.
This is the first study to compare patients with PD, DLB and AD at the time of diagnosis. It was found that t-α-syn can contribute as a teammate with tau in a CSF biomarker panel for PD and DLB, and strengthen the existing biomarker panel for AD.
帕金森病（PD）、路易体痴呆（DLB）和阿尔茨海默病（AD）是三种最常见的神经退行性疾病。由于症状重叠和共同的病理学，多达 20%的患者存在误诊。用于 AD 的脑脊液（CSF）生物标志物检测 panel 已进入临床应用，但用于 PD 和 DLB 的以及用于改善鉴别诊断的等效 panel 仍有待开发。本研究采用明确的基于社区的队列和经过验证的分析方法，评估了在新诊断的 PD、DLB 和 AD 患者中，CSF 总-α-突触核蛋白（t-α-syn）单独和与总 tau（t-tau）联合应用的诊断价值。
使用我们经过验证的内部酶联免疫吸附试验（ELISA）检测 78 名 PD 患者、20 名 AD 患者、19 名 DLB 患者和 32 名对照组的 CSF 中 t-α-syn 的浓度。使用商业化试剂盒检测 t-tau。采用受试者工作特征曲线（ROC）分析评估诊断性能。
与对照组（平均 517 pg/ml）相比，PD 患者（434 pg/ml，降低 16%，P=0.036）、DLB 患者（398 pg/ml，降低 23%，P=0.009）和 AD 患者（383 pg/ml，降低 26%，P=0.014）的 CSF t-α-syn 水平明显更低。PD、DLB 和 AD 患者之间的 t-α-syn 水平无显著差异。与单个标志物相比，t-tau/t-α-syn 比值具有更好的性能。
这是首次在诊断时比较 PD、DLB 和 AD 患者的研究。结果表明，t-α-syn 可与 tau 联合作为 PD 和 DLB 的 CSF 生物标志物检测 panel 的辅助指标，并增强现有的 AD 生物标志物检测 panel。
