The potential use of plasma NfL as a diagnostic and prognostic biomarker of fatigue in early Parkinson's disease

Background: Fatigue is a prevalent non-motor symptom that often appears in the early stages of Parkinson's disease (PD). Plasma neurofilament light chain (NfL) was elevated in PD patients and may be considered a potential biomarker for both motor and cognitive progression. Objectives: In this study, we explored the association between plasma NfL levels and various fatigue subtypes and the prediction of baseline plasma NfL levels for fatigue subtype conversion. Methods: Patients with PD were classified into four categories: persistent fatigue, never fatigue, non-persistent fatigue, and new-onset fatigue. They underwent detailed neurological evaluations at baseline and a 2-year follow-up. Plasma NfL, glial fibrillary acidic protein, phosphorylated tau181, amyloid beta 42, and A beta 40 levels in both PD patients and control subjects were measured using an ultrasensitive single molecule array. Results: The study enrolled 174 PD patients and 95 control subjects. Plasma NfL levels were significantly higher in the persistent fatigue group compared to the never fatigue group at the 2-year follow-up (p < 0.05). Longitudinally, 45.16% of baseline fatigue patients converted to non-fatigue at the 2-year follow-up. Additionally, 22.12% of patients initially without-figure patients converted to fatigue patients at the 2-year follow-up. Baseline plasma NfL levels were significantly higher in both the persistent fatigue and new-onset fatigue groups compared to the never fatigue group (p < 0.05). Higher baseline NfL levels were significantly associated with new-onset fatigue (odds ratio = 1.127, p = 0.034) after adjusting for confounders. Conclusion: Baseline plasma NfL levels may serve as a biomarker for predicting fatigue subtype conversion and the progression of fatigue in PD.