Serum neurofilament light as a biomarker for prognosis in patients with newly diagnosed Parkinson disease
medRxiv(2021)
摘要
Background Patients with Parkinson disease (PD) have variable disease progression. More accurate prediction of progression could improve clinical trial design. Although some variance in clinical progression can be predicted by age at onset and phenotype, we hypothesise that this can be improved by blood biomarkers. Objective To determine if serum neurofilament light (NfL) is a useful biomarker for prognostic modelling in PD. Methods We evaluated the relationship between serum NfL and baseline and longitudinal clinical measures as well as patients genetic (GBA and APOE) status in a large clinical dataset. We classified patients as having a favourable or an unfavourable outcome based on a previously validated model and explored whether serum NfL could distinguish prognostic phenotypes. We compared NfL with baseline candidate predictor variables and studied the combination of clinical, serum and genetic data. Results Serum NfL was associated with patients cognitive status at baseline. Baseline NfL was associated with the progression of motor and functional impairment and with increased mortality (Survival HR 1.85, CI: 1.03-3.33, p=0.04). Baseline NfL levels predicted unfavourable progression to a similar extent as previously validated clinical predictors (AUC: 0.74 vs 0.78, p=0.22). The combination of clinical, genetic and biomarker data produced a strong predication of unfavourable outcomes as compared to age and gender alone (AUC: 0.71-age/gender vs 0.83-ALL p = 0.0076) Conclusions Baseline serum NfL provides an objective measure of neurodegeneration in PD patients. Clinical trials of disease-modifying therapies might usefully stratify patients according using clinical, genetic and NfL status at the time of recruitment.
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关键词
neurofilament,parkinson,biomarker,light
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