Serum neurofilament light chain in LRRK2 related Parkinson's disease: A five years follow-up

Abstract

Background: Studies revealed that serum neurofilament light chain (NFL) levels not only increase considerably over time in Parkinson's disease (PD) but also have a significant association with disease progression. However, there is no evidence of the level of serum NFL in PD patients with leucine-rich repeat kinase 2 (LRRK2) mutation (LRRK2-PD) which is the most common mutation that causes familial and sporadic PD.Aim: Here we aimed to investigate the difference and longitudinal alteration of the serum level of NFL in LRRK2-PD and idiopathic PD (iPD) patients.Methods: We entered 228 iPD and 103 LRRK2-PD patients and 176 healthy controls (HCs) from PPMI. We compared the level of serum NFL at baseline, six months, one year, two years, three years, and five years visits. Also, we used linear mixed models to assess longitudinal changes of serum NFL over six months, one year, two years, three years, and five years within groups.Results: We found a significant difference in the level of serum NFL between three groups at baseline, two years, three years, and five years time points. Also, our analysis showed that LRRK2-PD patients had significantly lower serum NFL compared to iPD subjects at baseline. In the longitudinal analysis, there was no significant change in the HCs group over five years. The level of serum NFL was significantly increased after two, three, and five years from baseline in LRRK2-PD patients. Also, we found similar results for iPD subjects after three and five years from baseline.Conclusion: We can conclude that the overall neurodegeneration might be similar in LRRK2-PD and healthy subjects and lower than the idiopathic form of PD at the early stages, which may disappear in the later stages. Moreover, our findings suggest that the serum NFL might be a more accurate biomarker to distinguish iPD from healthy subjects rather than all PD patients or LRRK2-PD from healthy subjects at the early stages.