Quadalti Corinne, Calandra-Buonaura Giovanna, Baiardi Simone, Mastrangelo Andrea, Rossi Marcello, Zenesini Corrado, Giannini Giulia, Candelise Niccolò, Sambati Luisa, Polischi Barbara, Plazzi Giuseppe, Capellari Sabina, Cortelli Pietro, Parchi Piero
IRCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
NPJ Parkinsons Dis. 2021 Oct 11;7(1):93. doi: 10.1038/s41531-021-00232-4.
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）是帕金森综合征患者很有前景的生物标志物。我们评估了它们在区分帕金森病（PD）与非典型帕金森综合征（APD）方面的性能，并评估了NfL水平与疾病严重程度临床指标之间的关联。我们通过免疫测定法测量了帕金森病患者（n = 153）、多系统萎缩（MSA）患者（n = 80）、进行性核上性麻痹/皮质基底节综合征（PSP/CBS）患者（n = 58）、路易体痴呆患者（n = 64）、孤立性快速眼动睡眠行为障碍患者（n = 19）和孤立性自主神经功能衰竭患者（n = 30）脑脊液（CSF）和/或血浆中的NfL，以及通过实时震颤诱导转化（RT-QuIC）测量了CSF中的α-syn-s。疾病严重程度的指标包括病程、统一帕金森病评定量表第三部分（UPDRS-III）评分、霍恩和雅尔分期、体位性低血压、简易精神状态检查表（MMSE）评分以及CSF淀粉样β蛋白谱。APD患者的脑脊液NfL（cNfL）和血浆NfL（pNfL）水平均显著升高，并且能够与PD进行区分（与APD相比，cNfL曲线下面积（AUC）为0.96；pNfL AUC为0.95；与MSA相比，cNfL AUC为0.99；pNfL AUC为0.97；与PSP/CBS相比，cNfL AUC为0.94；pNfL AUC为0.94）。RT-QuIC在91.4%的PD患者中检测到α-syn-s，但在APD患者（均为MSA）中仅检测到2.5%。在PD/帕金森病痴呆（PDD）中，运动量表与cNfL水平显著相关。尽管pNfL以及cNfL和α-syn-s都能准确区分PD与APD，但CSF标志物的联合评估提供了比单独的RT-QuIC（与APD相比，p = 0.047；与MSA相比，p = 0.002；与PSP/CBS相比，p = 0.007）或单独的cNfL（与APD相比，p = 0.011；与MSA相比，p = 0.751；与PSP/CBS相比，p = 0.0001）更高的诊断价值（PD与APD相比，AUC为0.97；与MSA相比，AUC为0.97；与PSP/CBS相比，AUC为0.99）。这些结果支持在专科诊所使用这些检测方法。
