Center for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Department of Pathophysiology, Beijing Neurosurgical Institute, Beijing, China.
Eur J Neurol. 2023 Dec;30(12):3949-3967. doi: 10.1111/ene.16041. Epub 2023 Aug 28.
Alpha-synuclein seed amplification assays (α-syn SAAs) are promising diagnostic methods for Parkinson's disease (PD) and other synucleinopathies. However, there is limited consensus regarding the diagnostic and differential diagnostic performance of α-syn SAAs on biofluids and peripheral tissues.
A comprehensive research was performed in PubMed, Web of Science, Embase and Cochrane Library. Meta-analysis was performed using a random-effects model. A network meta-analysis based on an ANOVA model was conducted to compare the relative accuracy of α-syn SAAs with different specimens.
The pooled sensitivity and specificity of α-syn SAAs in distinguishing PD from healthy controls or non-neurodegenerative neurological controls were 0.91 (95% confidence interval [CI] 0.89-0.92) and 0.95 (95% CI 0.94-0.96) for cerebrospinal fluid (CSF); 0.91 (95% CI 0.86-0.94) and 0.92 (95% CI 0.87-0.95) for skin; 0.80 (95% CI 0.66-0.89) and 0.87 (95% CI 0.69-0.96) for submandibular gland; 0.44 (95% CI 0.30-0.59) and 0.92 (95% CI 0.79-0.98) for gastrointestinal tract; 0.79 (95% CI 0.70-0.86) and 0.88 (95% CI 0.77-0.95) for saliva; and 0.51 (95% CI 0.39-0.62) and 0.91 (95% CI 0.84-0.96) for olfactory mucosa (OM). The pooled sensitivity and specificity were 0.91 (95% CI 0.89-0.93) and 0.50 (95% CI 0.44-0.55) for CSF, 0.92 (95% CI 0.83-0.97) and 0.22 (95% CI 0.06-0.48) for skin, and 0.55 (95% CI 0.42-0.68) and 0.50 (95% CI 0.35-0.65) for OM in distinguishing PD from multiple system atrophy. The pooled sensitivity and specificity were 0.92 (95% CI 0.89-0.94) and 0.84 (95% CI 0.73-0.91) for CSF, 0.92 (95% CI 0.83-0.97) and 0.88 (95% CI 0.64-0.99) for skin and 0.63 (95% CI 0.52-0.73) and 0.86 (95% CI 0.64-0.97) for OM in distinguishing PD from progressive supranuclear palsy. The pooled sensitivity and specificity were 0.94 (95% CI 0.90-0.97) and 0.95 (95% CI 0.77-1.00) for CSF and 0.94 (95% CI 0.84-0.99) and 0.86 (95% CI 0.42-1.00) for skin in distinguishing PD from corticobasal degeneration.
α-Synuclein SAAs of CSF, skin, saliva, submandibular gland, gastrointestinal tract and OM are promising diagnostic assays for PD, with CSF and skin α-syn SAAs demonstrating higher diagnostic performance.
α-突触核蛋白种子扩增检测（α-syn SAAs）是帕金森病（PD）和其他突触核蛋白病有前景的诊断方法。然而，关于生物流体和外周组织中 α-syn SAAs 的诊断和鉴别诊断性能，尚未达成共识。
在 PubMed、Web of Science、Embase 和 Cochrane Library 中进行了全面的研究。使用随机效应模型进行荟萃分析。使用基于方差分析模型的网络荟萃分析比较了不同标本中 α-syn SAAs 的相对准确性。
脑脊液（CSF）中 α-syn SAAs 区分 PD 与健康对照或非神经退行性神经学对照的汇总敏感性和特异性分别为 0.91（95%置信区间 [CI] 0.89-0.92）和 0.95（95% CI 0.94-0.96）；皮肤为 0.91（95% CI 0.86-0.94）和 0.92（95% CI 0.87-0.95）；下颌下腺为 0.80（95% CI 0.66-0.89）和 0.87（95% CI 0.69-0.96）；胃肠道为 0.44（95% CI 0.30-0.59）和 0.92（95% CI 0.79-0.98）；唾液为 0.79（95% CI 0.70-0.86）和 0.88（95% CI 0.77-0.95）；嗅黏膜（OM）为 0.51（95% CI 0.39-0.62）和 0.91（95% CI 0.84-0.96）。CSF 的汇总敏感性和特异性分别为 0.91（95% CI 0.89-0.93）和 0.50（95% CI 0.44-0.55），皮肤为 0.92（95% CI 0.83-0.97）和 0.22（95% CI 0.06-0.48），OM 为 0.55（95% CI 0.42-0.68）和 0.50（95% CI 0.35-0.65），以区分 PD 与多系统萎缩。CSF 的汇总敏感性和特异性分别为 0.92（95% CI 0.89-0.94）和 0.84（95% CI 0.73-0.91），皮肤为 0.92（95% CI 0.83-0.97）和 0.88（95% CI 0.64-0.99），OM 为 0.63（95% CI 0.52-0.73）和 0.86（95% CI 0.64-0.97），以区分 PD 与进行性核上性麻痹。CSF 和皮肤的汇总敏感性和特异性分别为 0.94（95% CI 0.90-0.97）和 0.95（95% CI 0.77-1.00），以及 0.94（95% CI 0.84-0.99）和 0.86（95% CI 0.42-1.00），以区分 PD 与皮质基底节变性。
CSF、皮肤、唾液、下颌下腺、胃肠道和 OM 的 α-突触核蛋白 SAAs 是 PD 的有前途的诊断检测方法，CSF 和皮肤 α-syn SAAs 具有更高的诊断性能。
