Neurofilament light chain (NfL) and α-synuclein oligomeric seeds (α-syn-s) are promising biomarkers for patients with parkinsonism. We assessed their performance in discriminating Parkinson disease (PD) from atypical parkinsonisms (APDs) and evaluated the association between NfL levels and clinical measures of disease severity. We measured NfL in cerebrospinal fluid (CSF) and/or plasma by immunoassays and α-syn-s in CSF by real-time quaking-induced conversion (RT-QuIC) in patients with PD (n = 153), multiple system atrophy (MSA) (n = 80), progressive supranuclear palsy/cortico-basal syndrome (PSP/CBS) (n = 58), dementia with Lewy bodies (n = 64), isolated REM-sleep behaviour disorder (n = 19), and isolated autonomic failure (n = 30). Measures of disease severity included disease duration, UPDRS-III score, Hoehn and Yahr stage, orthostatic hypotension, MMSE score, and CSF amyloid-beta profile. Both CSF NfL (cNfL) and plasma NfL (pNfL) levels were markedly elevated in APDs, and allowed differentiation with PD (vs. APDs, cNfL AUC 0.96; pNfL AUC 0.95; vs. MSA cNfL AUC 0.99; pNfL AUC 0.97; vs. PSP/CBS cNfL AUC 0.94; pNfL AUC 0.94). RT-QuIC detected α-syn-s in 91.4% of PD, but only 2.5% of APDs (all MSA). In PD/PDD, motor scales significantly correlated with cNfL levels. Although pNfL and both cNfL and α-syn-s accurately distinguished PD from APDs, the combined assessment of CSF markers provided a higher diagnostic value (PD vs. APDs AUC 0.97; vs. MSA AUC 0.97; vs. PSP/CBS AUC 0.99) than RT-QuIC alone (p = 0.047 vs. APDs; p = 0.002 vs MSA; p = 0.007 vs PSP/CBS), or cNfL alone (p = 0.011 vs. APDs; p = 0.751 vs MSA; p = 0.0001 vs. PSP/CBS). The results support the use of these assays in specialised clinics.

神经丝轻链 (NfL) 和 α-突触核蛋白寡聚种子 (α-syn-s) 是帕金森病患者有希望的生物标志物。我们评估了他们在区分帕金森病 (PD) 和非典型帕金森综合征 (APD) 方面的表现，并评估了 NfL 水平与疾病严重程度的临床指标之间的关联。我们通过免疫测定法测量脑脊液 (CSF) 和/或血浆中的 NfL，并通过实时震颤诱导转化 (RT-QuIC) 测量脑脊液中的 α-syn-s，在 PD（n  = 153）、多系统萎缩患者中（ MSA) ( n  = 80)、进行性核上性麻痹/皮质基底综合征 (PSP/CBS) ( n  = 58)、路易体痴呆 ( n  = 64)、孤立性快速眼动睡眠行为障碍 ( n = 19) 和孤立的自主神经衰竭 ( n = 30）。疾病严重程度的测量包括疾病持续时间、UPDRS-III 评分、Hoehn 和 Yahr 分期、直立性低血压、MMSE 评分和 CSF 淀粉样蛋白-β 谱。CSF NfL (cNfL) 和血浆 NfL (pNfL) 水平在 APD 中均显着升高，并允许与 PD 分化（与 APD 相比，cNfL AUC 0.96；pNfL AUC 0.95；与 MSA cNfL AUC 0.99；pNfL AUC 0.97 相比） PSP/CBS cNfL AUC 0.94；pNfL AUC 0.94）。RT-QuIC 在 91.4% 的 PD 中检测到 α-syn-s，但只有 2.5% 的 APD（所有 MSA）。在 PD/PDD 中，运动量表与 cNfL 水平显着相关。尽管 pNfL 以及 cNfL 和 α-syn-s 都能准确地区分 PD 和 APD，但 CSF 标志物的联合评估提供了更高的诊断价值（PD 与 APD AUC 0.97；与 MSA AUC 0.97；与 PSP/CBS AUC 0.99）比单独的 RT-QuIC ( p  = 0.047 vs. APDs; p = 0.002 与 MSA；p  = 0.007 对比 PSP/CBS），或单独的 cNfL（p  = 0.011 对比 APD；p  = 0.751 对比 MSA；p  = 0.0001 对比 PSP/CBS）。结果支持在专科诊所使用这些检测。