Age-Related Normative Data and Percentile Ranges for Serum Neurofilament Light Chain Levels

Introduction: Blood-based neurofilament light chain (NfL), a neuronal cytoskeleton protein, has proven to be a dynamic and robust biomarker for neurodegeneration. The influence of age on NfL levels has been extensively documented in cerebrospinal fluid studies, with blood quantification showing similar trends. To aid the clinical interpretation of NfL values, it is crucial to establish normal reference intervals through population-specific studies that account for NfL’s dynamic range. Methods: In this study, we determined reliable age-stratified reference values for serum NfL (sNfL) using the single-molecule array (SiMoA) immunoassay in individuals with no evidence of cognitive impairment according to age- and education-adjusted normative data for the Mini-Mental State Examination (MMSE), recruited from the central region of Portugal, across a broad age range. Results: Our sample comprised 335 individuals (median age of 53 years, 57% female) aged 20 to 99 years. We found a strong correlation between age and sNfL levels (rho=0.72, p<0.001). Age-stratified reference limits (upper 95th percentile in each decade) were established as follows: 20-30 years= 9.77 pg/mL; 31-40 years= 13.3 pg/mL; 41-50 years= 16.5 pg/mL; 51-60 years= 21.2 pg/mL; 61-70 years= 41.3 pg/mL; 71-80 years= 48.1 pg/mL; 80+ years= 62.5 pg/mL. Conclusion: These findings provide a unique national normative baseline for the Portuguese population.