Utility of Plasma Neurofilament Light As a Diagnostic and Prognostic Biomarker of the Postural Instability Gait Disorder Motor Subtype in Early Parkinson's Disease

Overview

Journal Mol Neurodegener

Publisher Biomed Central

Specialties Molecular Biology
Neurology

Date 2020 Jun 7

PMID 32503574

Citations 33

Authors

Adeline Su Lyn Ng

Yi Jayne Tan

Alisa Cui Wen Yong

Seyed Ehsan Saffari

Zhonghao Lu

Ebonne Yulin Ng

Samuel Yong Ern Ng

Nicole Shuang Yu Chia

Xinyi Choi

Dede Heng

Shermyn Neo

Zheyu Xu

Nicole Chwee Har Keong

Kay Yaw Tay

Wing Lok Au

Louis Chew Seng Tan

Eng-King Tan

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Citing Articles

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