Clinica Neurologica, Università degli Studi di Perugia Perugia, Italy.
Clinica Neurologica, Università degli Studi di Perugia Perugia, Italy ; Dipartimento di Epidemiologia, Regione Umbria Perugia, Italy.
Front Aging Neurosci. 2014 Mar 31;6:53. doi: 10.3389/fnagi.2014.00053. eCollection 2014.
There is a great interest in developing cerebrospinal fluid (CSF) biomarkers for diagnosis and prognosis of Parkinson's disease (PD). CSF alpha synuclein (α-syn) species, namely total and oligomeric α-syn (t-α-syn and o-α-syn), have shown to be of help for PD diagnosis. Preliminary evidences show that the combination of CSF t-α-syn and classical Alzheimer's disease (AD) biomarkers-β-amyloid 1-42 (Aβ42), total tau (t-tau), phosphorylated tau (p-tau)-differentiate PD patients from controls, and that reduced levels of Aβ42 represent a predictive factor for development of cognitive deterioration in PD. In this prospective study carried out in 44 PD patients and 25 neurological controls we wanted to verify whether the combination of CSF α-synuclein species-t-α-syn and o-α-syn-and classical AD biomarkers may help in differentiating PD from neurological controls, and if these biomarkers may predict cognitive decline. The median of follow-up duration was 3 years (range: 2-6 years). Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used for monitoring cognitive changes along time, being administered once a year. Oligo/total α-syn ratio (o/t-α-syn ratio) confirmed its diagnostic value, significantly contributing to the discrimination of PD from neurological controls. A greater diagnostic accuracy was reached when combining o/t-α-syn and Aβ42/tau ratios (Sens = 0.70, Spec = 0.84, AUC = 0.82; PPV = 0.89, NPV = 0.62, LR+ = 4.40, DOR = 12.52). Low CSF Aβ42 level was associated with a higher rate of MMSE and MoCA decline, confirming its role as independent predictive factor for cognitive decline in PD. None of the other biomarkers assessed (t-tau, p-tau, t-α-syn and o-α-syn) showed to have prognostic value. We conclude that combination of CSF o/t-α-syn and Aβ42/tau ratios improve the diagnostic accuracy of PD. PD patients showing low CSF Aβ42 levels at baseline are more prone to develop cognitive decline.
人们对于开发用于诊断和预测帕金森病（PD）的脑脊液（CSF）生物标志物有着浓厚的兴趣。CSF 中的α-突触核蛋白（α-syn），即总α-突触核蛋白（t-α-syn）和寡聚体α-突触核蛋白（o-α-syn），已被证明有助于 PD 的诊断。初步证据表明，CSF t-α-syn 与经典的阿尔茨海默病（AD）生物标志物-β-淀粉样蛋白 1-42（Aβ42）、总tau（t-tau）和磷酸化 tau（p-tau）的结合可以区分 PD 患者和对照组，并且 Aβ42 水平降低代表 PD 患者认知恶化的预测因素。在这项在 44 名 PD 患者和 25 名神经科对照组中进行的前瞻性研究中，我们想验证 CSF α-synuclein 物种-t-α-syn 和 o-α-syn-与经典 AD 生物标志物的组合是否有助于区分 PD 与神经科对照组，以及这些生物标志物是否可以预测认知下降。中位随访时间为 3 年（范围：2-6 年）。使用简易精神状态检查（MMSE）和蒙特利尔认知评估（MoCA）来监测认知随时间的变化，每年进行一次评估。寡聚体/总α-syn 比值（o/t-α-syn 比值）证实了其诊断价值，对区分 PD 与神经科对照组有显著贡献。当组合使用 o/t-α-syn 和 Aβ42/tau 比值时，诊断准确性更高（灵敏度为 0.70，特异性为 0.84，AUC 为 0.82；阳性预测值为 0.89，阴性预测值为 0.62，阳性似然比为 4.40，优势比为 12.52）。CSF Aβ42 水平较低与 MMSE 和 MoCA 下降率较高有关，证实了其作为 PD 认知下降的独立预测因素的作用。评估的其他生物标志物（t-tau、p-tau、t-α-syn 和 o-α-syn）均未显示出预后价值。我们得出结论，CSF o/t-α-syn 和 Aβ42/tau 比值的组合可提高 PD 的诊断准确性。基线时 CSF Aβ42 水平较低的 PD 患者更易发生认知下降。
