Ng Adeline Su Lyn, Tan Yi Jayne, Yong Alisa Cui Wen, Saffari Seyed Ehsan, Lu Zhonghao, Ng Ebonne Yulin, Ng Samuel Yong Ern, Chia Nicole Shuang Yu, Choi Xinyi, Heng Dede, Neo Shermyn, Xu Zheyu, Keong Nicole Chwee Har, Tay Kay Yaw, Au Wing Lok, Tan Louis Chew Seng, Tan Eng-King
Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Bukit Merah, 308433, Singapore.
Neuroscience and Behavioural Disorders Program, Duke-NUS Medical School, 8 College Road, Bukit Merah, 169857, Singapore.
Mol Neurodegener. 2020 Jun 5;15(1):33. doi: 10.1186/s13024-020-00385-5.
The main motor subtypes of Parkinson's disease (PD) include tremor-dominant (TD) and postural instability gait disorder (PIGD), with varying disease course that warrant the development of biomarkers capable of predicting progression according to motor subtype. The PIGD subtype is associated with a poorer prognosis, hence identification of a biomarker associated with PIGD is clinically relevant. Neurofilament light (NfL) chain is a potential biomarker of disease severity in neurological disorders including PD. However, no study has investigated NfL and PD motor subtypes. Here, we aimed to investigate the diagnostic and prognostic utility of plasma NfL for PD motor subtypes in early Parkinson's disease. Given the higher risk for cognitive and motor decline in PIGD, we hypothesized that plasma NfL is a potential biomarker for PIGD.
Plasma NfL was measured in 199 participants (149 PD and 50 healthy controls, HC) using an ultrasensitive single molecule array. Patients were classified into TD or PIGD based on MDS-UPDRS components. After 2 years, 115 patients were reassessed. Association between NfL and clinical measures in PIGD and TD at baseline and at 2-year follow-up were analysed.
At baseline, plasma NfL levels were higher in PD than HC (8.8 ± 3.4 vs 16.2 ± 7.6 pg/ml, p < 0.0001), and differentiated PD from HC with a good diagnostic accuracy (AUC = 0.833, p < 0.001). At 2 years, NfL was higher in PIGD than TD (18.4 ± 14.5 vs 12.6 ± 4.4 pg/ml, p = 0.039). Within the PIGD group, higher NfL associated significantly with worse global cognition and UPDRS motor scores at baseline, and was able to predict motor and cognitive decline at a mean follow-up duration of 1.9 years, controlled for age, sex and disease duration.
In this longitudinal study, we demonstrated for the first time the potential utility of plasma NfL as a diagnostic and prognostic biomarker in PIGD even at early stages of PD. These important novel findings will require further confirmation in larger, longitudinal PD cohorts.
帕金森病（PD）的主要运动亚型包括震颤为主型（TD）和姿势不稳步态障碍型（PIGD），其病程各异，这就需要开发能够根据运动亚型预测疾病进展的生物标志物。PIGD亚型的预后较差，因此，识别与PIGD相关的生物标志物具有临床意义。神经丝轻链（NfL）是包括PD在内的神经系统疾病中疾病严重程度的潜在生物标志物。然而，尚无研究调查NfL与PD运动亚型之间的关系。在此，我们旨在研究血浆NfL对早期帕金森病患者PD运动亚型的诊断和预后价值。鉴于PIGD患者认知和运动功能下降的风险较高，我们推测血浆NfL是PIGD的潜在生物标志物。
使用超灵敏单分子阵列检测了199名参与者（149例PD患者和50名健康对照者，HC）的血浆NfL。根据MDS-UPDRS成分将患者分为TD型或PIGD型。2年后，对115名患者进行了重新评估。分析了基线和2年随访时PIGD和TD患者中NfL与临床指标之间的关联。
在基线时，PD患者的血浆NfL水平高于HC（8.8±3.4 vs 16.2±7.6 pg/ml，p<0.0001），并且以良好的诊断准确性将PD与HC区分开来（AUC=0.833，p<0.001）。在2年时，PIGD患者的NfL水平高于TD患者（18.4±14.5 vs 12.6±4.4 pg/ml，p=0.039）。在PIGD组中，较高的NfL水平在基线时与较差的整体认知和UPDRS运动评分显著相关，并且能够在平均随访1.9年时预测运动和认知功能下降，同时控制了年龄、性别和病程。
在这项纵向研究中，我们首次证明了即使在PD的早期阶段，血浆NfL作为PIGD的诊断和预后生物标志物的潜在价值。这些重要的新发现需要在更大规模的纵向PD队列中进一步证实。
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