Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Doha, Qatar.
College of Health and Life Sciences, Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha, Qatar.
Mov Disord. 2021 Sep;36(9):2048-2056. doi: 10.1002/mds.28611. Epub 2021 May 12.
Tangible efforts have been made to identify biomarkers for Parkinson's disease (PD) diagnosis and progression, with α-synuclein (α-syn) related biomarkers being at the forefront.
The objectives of this study were to explore whether cerebrospinal fluid (CSF) levels of total, oligomeric, phosphorylated Ser 129 α-synuclein, along with total tau, phosphorylated tau 181, and β-amyloid 1-42 are (1) informative as diagnostic markers for PD, (2) changed over disease progression, and/or (3) correlated with motor and cognitive indices of disease progression in the longitudinal De Novo Parkinson cohort.
A total of 94 de novo PD patients and 52 controls at baseline and 24- and 48-month follow-up were included, all of whom had longitudinal lumbar punctures and clinical assessments for both cognitive and motor functions. Using our in-house enzymelinked immunosorbent assays and commercially available assays, different forms of α-synuclein, tau, and β-amyloid 1-42 were quantified in CSF samples from the De Novo Parkinson cohort.
Baseline CSF total α-synuclein was significantly lower in early de novo PD compared with healthy controls, whereas the ratio of oligomeric/total and phosphorylated/total were significantly higher in the PD group. CSF oligomeric-α-synuclein longitudinally increased over the 4-year follow-up in the PD group and correlated with PD motor progression. Patients at advanced stages of PD presented with elevated CSF oligomeric-α-synuclein levels compared with healthy controls.
Longitudinal transitions of CSF biomarkers over disease progression might not occur linearly and are susceptible to disease state. CSF oligomeric-α-synuclein levels appear to increase with diseases severity and reflect PD motor rather than cognitive trajectories. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
为了诊断和监测帕金森病（PD）的进展，已经做出了许多努力来寻找生物标志物，其中α-突触核蛋白（α-syn）相关生物标志物处于领先地位。
本研究旨在探索脑脊液（CSF）中总α-突触核蛋白、寡聚体α-突触核蛋白、磷酸化 Ser129 型α-突触核蛋白、总tau 蛋白、磷酸化 tau 181 型、β-淀粉样蛋白 1-42 的水平是否：（1）作为 PD 的诊断标志物具有信息性；（2）随疾病进展而变化；和/或（3）与纵向 De Novo Parkinson 队列中疾病进展的运动和认知指标相关。
本研究共纳入 94 例新发 PD 患者和 52 例对照组，所有患者在基线和 24 个月、48 个月时均进行了纵向腰椎穿刺和认知与运动功能的临床评估。使用我们的酶联免疫吸附测定法和商业上可获得的测定法，在 De Novo Parkinson 队列的 CSF 样本中定量检测不同形式的α-突触核蛋白、tau 和β-淀粉样蛋白 1-42。
与健康对照组相比，早期新发 PD 患者的 CSF 总α-突触核蛋白水平显著降低，而 PD 组的寡聚体/总α-突触核蛋白和磷酸化/总α-突触核蛋白的比值显著升高。在 PD 组中，CSF 寡聚体-α-突触核蛋白在 4 年的随访过程中呈纵向增加趋势，与 PD 运动进展相关。与健康对照组相比，处于 PD 晚期的患者具有更高的 CSF 寡聚体-α-突触核蛋白水平。
随着疾病的进展，CSF 生物标志物的纵向转变可能不会呈线性发生，并且容易受到疾病状态的影响。CSF 寡聚体-α-突触核蛋白水平似乎随着疾病严重程度的增加而增加，反映了 PD 的运动而不是认知轨迹。
