Department of Systems Medicine, University of Roma Tor Vergata, Rome, Italy.
IRCCS Fondazione Santa Lucia, Rome, Italy; Department of Experimental Medicine and Surgery, University of Roma Tor Vergata, Rome, Italy.
Parkinsonism Relat Disord. 2019 Apr;61:203-206. doi: 10.1016/j.parkreldis.2018.10.018. Epub 2018 Oct 15.
Although non-motor symptoms are early and disabling features of PD, reliable predictors and effective therapies are not yet available. Measurement of CSF proteins mirroring brain pathology is currently utilized for diagnostic and prognostic clustering of patients with neurodegenerative diseases but the association with non-motor symptoms in PD has not been evaluated. Here we performed a cross-sectional correlation study, aimed at identifying potential fluid biomarkers for non-motor symptoms in PD.
CSF levels of 42-amyloid-β, total and phosphorylated tau, α-synuclein and reciprocal ratios were measured in a group of 46 PD patients compared to 37 gender/age-matched controls and correlated with standard clinical scores for motor and non-motor features.
We observed that α-synuclein levels were reduced in PD (p < 0.05, AUC = 0.8; p < 0.05) and inversely correlated with non-motor symptoms scale total score and items 3 and 9, even independently from age, disease duration, motor impairment severity and dopaminergic treatment (T = -2,9, p < 0.014; T = -3.6, p < 0.05; item 9: T = -2.1, p < 0.05, respectively).
Our findings suggest that the reduction of CSF α-synuclein may parallel degeneration of non-dopaminergic systems. Although confirmatory studies are necessary, CSF α-synuclein reduction might represent a potential biomarker to monitor non-motor symptoms burden.
尽管非运动症状是 PD 的早期和致残特征,但目前还没有可靠的预测指标和有效的治疗方法。反映大脑病理的 CSF 蛋白测量目前用于神经退行性疾病患者的诊断和预后聚类,但尚未评估其与 PD 中非运动症状的关联。在这里,我们进行了一项横断面相关性研究,旨在确定 PD 中非运动症状的潜在液体生物标志物。
我们比较了 46 名 PD 患者和 37 名性别/年龄匹配的对照组的 CSF 中 42-淀粉样蛋白-β、总tau 和磷酸化 tau、α-突触核蛋白和相互比值的水平,并与运动和非运动特征的标准临床评分相关联。
我们观察到α-突触核蛋白水平在 PD 中降低(p < 0.05,AUC = 0.8;p < 0.05),并且与非运动症状量表总分和第 3 项和第 9 项呈负相关,甚至独立于年龄、疾病持续时间、运动障碍严重程度和多巴胺治疗(T = -2.9,p < 0.014;T = -3.6,p < 0.05;第 9 项:T = -2.1,p < 0.05,分别)。
我们的发现表明 CSF α-突触核蛋白的减少可能与非多巴胺能系统的退化平行。尽管需要进一步的验证性研究,但 CSF α-突触核蛋白的减少可能代表监测非运动症状负担的潜在生物标志物。