Objective: To identify systematically  studies evaluating CSF, serum, and plasma NfL as a prognostic factor for clinical progression in PD and  to describe study characteristics and evaluate risk of bias; and to summarise evidence on the association between CSF, serum, or plasma NfL and motor and cognitive outcomes during longitudinal follow-up.

Background: Parkinson’s disease (PD) is a heterogeneous neurodegenerative disorder with variable progression. Neurofilament light chain (NfL) is a marker of axonal damage measurable in blood and CSF and a candidate prognostic biomarker for PD motor progression.

Method: A systematic review of prospective and retrospective longitudinal cohort studies was conducted. Adult PD patients diagnosed by valid criteria were included with no restriction on age, disease duration, or medication status. Studies required minimum 12-month follow-up reporting NfL as a continuous or categorical prognostic variable. Atypical parkinsonism and combined biomarker panel studies were excluded. Risk of bias was assessed using the Quality In Prognosis Studies tool and certainty of evidence rated using GRADE methodology.

Results: Fourteen studies enrolling  2,100 PD patients were included. For continuous UPDRS-III motor severity, of the ten studies including 1,918 participants  seven  reported significant associations between higher baseline NfL and faster motor decline; three studies found no significant association after full covariate adjustment. All six studies with 910 participants  demonstrated significant associations between higher baseline CSF NfL and faster motor progression, with the largest effect sizes in cohorts with follow-up exceeding five years. Three studies enrolling 679 PD patients reported significant associations between higher baseline NfL and discrete motor milestones, including freezing of gait, nursing home admission, and Hoehn & Yahr stage 5, with hazard ratios ranging from 1.57 to 6.16. GRADE certainty was very low for continuous UPDRS-III prediction and low for motor milestones .

Conclusion: Our results suggest prognostic utility of serum, plasma, and CSF NfL for motor progression in PD; however, evidence certainty is low. Future studies require pre-registered analysis plans, blinded outcome assessment, independent cohort validation, standardisation of NfL reporting thresholds, and  covariate adjustment strategies to reduce risk of bias.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neurofilament-light-chain-as-a-prognostic-marker-of-motor-progression-in-parkinsons-disease-a-systematic-review/