Increased Serum Neurofilament Light Chain Levels in Parkinson's Disease Patients Carrying the p.A53T SNCA Mutation: Data from the Parkinson's Progression Markers Initiative Study.

BACKGROUND

Serum neurofilament light chain (NfL) levels, a marker of axonal damage, are generally elevated in neurodegenerative conditions, but results in idiopathic Parkinson's disease (iPD) have been inconsistent. The p.A53T SNCA mutation usually leads to a severe form of PD.

OBJECTIVE

The aim of this work was to assess the possible use of serum NfL as a marker of ongoing neurodegeneration in A53T-PD.

METHODS

Using a propensity score matching-based technique with data from the Parkinson's Progression Markers Initiative, we matched, in a 3:1 ratio, A53T-PD participants to iPD patients and healthy control subjects (HCs) by age and disease duration, where applicable.

RESULTS

After matching, 18 A53T-PD, 54 iPD, and 54 HC subjects were analyzed. Serum NfL was higher in A53T-PD (9.82 [8.02-18.1] pg/ml) compared with HCs (7.54 [5.76-10.1], P = 0.008) or iPD patients (8.59 [6.86-11.1], P = 0.077) (overall P = 0.049).

CONCLUSIONS

A53T-PD patients have high NfL levels, which could potentially be used as an outcome in clinical trials with disease-modifying agents. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.