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

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Abstract 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. 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 two-year follow-up. Plasma NfL, GFAP, p-tau181, Aβ42, and Aβ40 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 two-year follow-up (P＜0.05). Longitudinally, 45.16% of baseline fatigue patients converted to non-fatigue at two-year follow-up. Additionally, 22.12% of patients initially without-figure patients converted to fatigue patients at two-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 plasma NfL levels were significantly associated with the conversion to the non-fatigue subtype (OR=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.

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