Abstract Background HSP‐ SPG11 and HSP‐ ZFYVE26 are autosomal‐recessive forms of hereditary spastic paraplegias (HSPs). As therapeutic trials emerge, validated biomarkers are critically needed. Objectives To evaluate plasma neurofilament light chain (pNfL) as a biomarker for neurodegeneration and disease progression. Methods We analyzed pNfL levels in 57 patients (36 HSP‐ SPG11 , 21 HSP‐ ZFYVE26 ) and matched controls using single‐molecule array technology. Longitudinal clinical and biomarker data were collected over 5 years. Results Baseline pNfL levels were significantly elevated in patients: 33.85 pg/mL (IQR 25.15–47.38) in HSP‐ SPG11 , 46.70 pg/mL (IQR 29.95–54.84) in HSP‐ ZFYVE26 , and 4.90 pg/mL (IQR 3.48–6.90) in controls ( P < 0.001). No significant difference was observed between HSP‐ SPG11 and HSP‐ ZFYVE26 . In matched pair analysis, pNfL showed inverse correlation with age (ρ = −0.463, P < 0.001). Baseline pNfL did not predict future clinical progression. Conclusions Elevated pNfL reflects early neuroaxonal injury in HSP‐ SPG11 and HSP‐ ZFYVE26 ; however, it could not be used as a surrogate for disease progression. © 2025 International Parkinson and Movement Disorder Society.
Agianda et al. (Tue,) studied this question.