Neurofilament light as a biomarker for motor decline in Parkinson’s disease

Abstract

ObjectivesThe aim of this study was to determine whether neurofifilament light (NfL) could reflect motor decline and compare the predictive values of cerebrospinal fluid (CSF) and serum NfL in individuals with PD.MethodsCSF/serum samples were collected from patients with PD and healthy controls (HCs) with motor assessments at baseline and after three years of follow-up from the Parkinson’s Progression Markers Initiative (PPMI). Multiple linear regression models and linear mixed-effects models were used to investigate the associations of motor assessments with baseline and longitudinal CSF/serum NfL. Associations between the change rates of motor assessments and CSF/serum NfL were further investigated via multiple linear regression models. Mediating effect analysis was used to research whether CSF alpha-synuclein (α-syn) acts as the mediator between NfL and motor assessments.ResultsWe found patients with PD had higher baseline CSF/serum NfL levels than HCs. Both baseline CSF/serum NfLs and their change rates predicted measurable motor decline in PD assessed by different motor scores. Baseline serum NfL and its rate of change were strongly associated with CSF NfL levels in patients with PD (P < 0.001). Besides, there were also significant differences in CSF/serum NfL levels and predicted values of motor decline between men and women with PD. Mediating effect analysis showed CSF α-syn mediated the effect of CSF NfL on total Unified Parkinson’s Disease Rating Scale (UPDRS) scores and UPDRSIII with 30.6 and 20.2% mediation, respectively.ConclusionOur results indicated that NfL, especially serum NfL concentration, could serve as an easily accessible biomarker to monitor the severity and progression of motor decline in individuals with PD, especially in men with PD. Besides, CSF α-syn acts as a mediator between NfL and motor progression.

Brain-Biomarker Changes in Body Fluids of Patients with Parkinson’s Disease

“…Similar results were obtained in another large study [ 36 ], in which PD patients were selected on the basis of diagnosis within 2 years, not receiving treatment at baseline, Hoehn and Yahr (H-Y) stage 1 or 2, 123I-isoflurane DaT imaging, and, to avoid misdiagnosis, a longitudinal review of their diagnosis. The study included CSF samples from 207 PD patients and 102 controls, while the sera were collected from 361 PD patients and 176 controls, plus 291 individuals who provided both serum and CSF samples.…”

Plasma proteomic profiling identifies CD33 as a marker of HIV control in natural infection and after therapeutic vaccination

“…3 i, ADAM15 rho = 0.9696 p < 0.0001, GGT5 rho = 0.9195 p = 0.0002 and NEFL rho = 0.9223 p = 0.0001, Spearman rank test). Interestingly, the NEFL protein, is a well-established marker for neurological damage in several diseases, 19 , 20 and tend to increase the levels during MAP phase. These changes did not reach statistical significant difference between MAP-C and MAP-NC groups ( Supplementary Figure S3d and S3e , Wilcoxon rank test and Mann–Whitney test, respectively).…”

Search for Molecular Biomarkers of Parkinson’s Disease. New Tissues and Methods

“…They seem to be higher in more advanced PD patients compared to controls, while controversial data were obtained for early disease stages (6). Heterogeneous data were obtained with respect to association of blood NFL concentrations with motor impairment in PD, revealing both positive (30,34,35) and negative results (36) while consistent positive association between baseline blood NFL levels and negative cognitive outcome have been reported (30,36,37).…”