Serum neurofilament light chain levels reflect cortical neurodegeneration in de novo Parkinson's disease

• Published in: Parkinsonism & related disorders Vol. 74; pp. 43 - 49
• Main Authors: Sampedro, Frederic, Pérez-González, Rocío, Martínez-Horta, Saul, Marín-Lahoz, Juan, Pagonabarraga, Javier, Kulisevsky, Jaime
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-05-2020
• Subjects: Aged; Biomarkers; Cerebral Cortex - diagnostic imaging; Cerebral Cortex - pathology; Cognitive decline; Cognitive Dysfunction - etiology; Cognitive Dysfunction - physiopathology; Cortical thinning; Cross-Sectional Studies; Disease Progression; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Neurofilament Proteins - blood; NfL; Parkinson Disease - blood; Parkinson Disease - complications; Parkinson Disease - diagnosis; Parkinson Disease - pathology; Parkinson's disease; Cognitive decline; Biomarkers; Parkinson's disease; Cortical thinning; NfL
• ISSN: 1353-8020; 1873-5126
• DOI: 10.1016/j.parkreldis.2020.04.009

Cognitive impairment and dementia are highly prevalent non-motor complications in Parkinson's disease (PD) with deleterious consequences for patients and caregivers. With no treatment currently available, finding and validating minimally-invasive biomarkers of neurodegeneration in this population represents an urgent need for clinical trials targeting its prevention or delay. Recently, serum neurofilament light chain (NfL) levels have been identified as a promising biomarker of neural loss, but whether they reflect cortical neurodegeneration in early PD stages has not been addressed.
From the Parkinson's Progression Markers Initiative (PPMI), we selected 133 de novo PD patients and 56 healthy controls (HC) with available structural neuroimaging and serum NfL data. We then studied whether NfL levels were abnormal in the PD group with respect to HC, and whether they correlated with cognitive indicators and cortical macro (cortical thinning) and microstructural (increased intracortical mean diffusivity) degeneration.
Serum NfL levels were significantly increased in the PD group (p = 0.010), and were also related to worse cognitive performance and a cortical macro and microstructural compromise (p < 0.05 corrected). These associations were observed both cross-sectionally and longitudinally within a one-year follow-up period. Topographically, NfL levels reflected posterior-cortical deterioration rather than frontal damage. Importantly, NfL levels were not associated with striatal SPECT-DAT uptake or β-amyloid burden.
Our results show that serum NfL levels reflect cortical neurodegeneration from the very early stages of PD. Moreover, its brain structural correlates and its lack of relationship with dopaminergic depletion or amyloidosis suggests that NfL could track the underlying pathological process leading to PD dementia.
•Cognitive decline is a frequent non-motor complication in Parkinson's disease (PD).•Finding and validating biomarkers of early neurodegeneration is needed in PD.•Serum NfL levels reflect cortical neurodegeneration from the very early stages of PD.•Serum NfL could track the underlying pathological process leading to PD dementia.