Abstract
BackgroundThe 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.MethodsPlasma 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.ResultsAt 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.ConclusionsIn 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.
Highlights
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
Ng et al Molecular Neurodegeneration (2020) 15:33 (Continued from previous page). In this longitudinal study, we demonstrated for the first time the potential utility of plasma Neurofilament light (NfL) as a diagnostic and prognostic biomarker in PIGD even at early stages of PD
receiver operating characteristic (ROC) analysis showed that plasma NfL could discriminate PD from Healthy controls (HC) with area under the curve (AUC): 0.833, 95% CI: 0.774–0.893, sensitivity = 60%, specificity = 90%; Fig. 2)
Summary
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. Neurofilament light (NfL) chain is a potential biomarker of disease severity in neurological disorders including PD. 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. Out of the neurofilament proteins, neurofilament light (NfL) chain has been recognized as a possible marker of axonal injury in various neurological disorders [1], including multiple sclerosis [2], motor neurone disease [3, 4], frontotemporal dementia spectrum disorders [5, 6], traumatic brain injury [7], and cerebrovascular disease [8]. NfL has been found to associate with longer disease duration, more aggravated motor symptoms [11], and correlate with motor and/or cognitive decline [13] in PD
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