Abstract
Background:The objective of this study was to assess neurofilament light chain as a Parkinson’s disease biomarker.Methods:We quantified neurofilament light chain in 2 independent cohorts: (1) longitudinal cerebrospinal fluid samples from the longitudinal de novo Parkinson’s disease cohort and (2) a large longitudinal cohort with serum samples from Parkinson’s disease, other cognate/neurodegenerative disorders, healthy controls, prodromal conditions, and mutation carriers.Results:In the Parkinson’s Progression Marker Initiative cohort, mean baseline serum neurofilament light chain was higher in Parkinson’s disease patients (13 ± 7.2 pg/mL) than in controls (12 ± 6.7 pg/mL), P = 0.0336. Serum neurofilament light chain increased longitudinally in Parkinson’s disease patients versus controls (P < 0.01). Motor scores were positively associated with neurofilament light chain, whereas some cognitive scores showed a negative association.Conclusions:Neurofilament light chain in serum samples is increased in Parkinson’s disease patients versus healthy controls, increases over time and with age, and correlates with clinical measures of Parkinson’s disease severity. Although the specificity of neurofilament light chain for Parkinson’s disease is low, it is the first blood-based biomarker candidate that could support disease stratification of Parkinson’s disease versus other cognate/neurodegenerative disorders, track clinical progression, and possibly assess responsiveness to neuroprotective treatments. However, use of neurofilament light chain as a biomarker of response to neuroprotective interventions remains to be assessed.
Highlights
neurofilament light chain (NfL) measurements were obtained in the Cerebrospinal fluid (CSF) of 176 participants, including (1) newly diagnosed, drug-naive Parkinson’s disease (PD) patients; (2) age, sex, and education-matched healthy controls (HCs); and (3) participants who were initially enrolled as having PD but on clinical follow-up had their diagnoses revised to a cognate or neurodegenerative disorder (OND; for details, see Supplement)
In a second exploratory step, we analyzed a crosssectional bridging cohort in which CSF and serum NfL levels were measured as a bridging step between the CSF samples measured in DeNoPa and the serum samples analyzed in Parkinson’s Progression Marker Initiative (PPMI)
The strong correlation between CSF and serum NfL encouraged us to move to the validation step using serum samples from the longitudinal PPMI cohort
Summary
: Background: The objective of this study was to assess neurofilament light chain as a Parkinson’s disease biomarker
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