Pathological separation utility of plasma neurofilament light chain (NfL) detected by a single-molecule immunoassay platform in neurodegenerative diseases
- 1Tianjin Hospital, Tianjin, China
- 2Tianjin KingMed Diagnostics Laboratory Co. Ltd, Tianjin, China
- 3Tianjin Key Laboratory of Multi-omics Precision Diagnosis Technology for Neurological Diseases, Tianjin, China
Abstract
Background: To establish age-stratified plasma neurofilament light chain (NfL) reference intervals using a domestic Digital Single-Molecule Sensing (DiSMS) platform and to explore neuropathological profiles across amyotrophic lateral sclerosis (ALS), inflammatory demyelinating diseases (IDD) and healthy individuals.
Methods: We enrolled 719 participants (510 healthy controls, 121 ALS, 88 IDD). Age-specific reference intervals defining the healthy boundary were established using the 2.5th–97.5th percentile method. Pathological separation utility was evaluated via age-stratified subgroup comparisons and receiver operating characteristic (ROC) analysis.
Results: Plasma NfL levels in healthy individuals increased significantly with age (p<0.0001), with reference intervals of 2.68–17.09 pg/mL (20–49 years), 7.14–61.95 pg/mL (50–69 years) and 14.20–104.71 pg/mL (≥70 years). Out-of-boundary NfL elevation rates demonstrated prominent age-dependent fluctuations. In ALS, out-of-boundary elevation rates were 98.3% (57/58) for the 20–49 age group, 68.4% (39/57) for the 50–69 group and 50.0% (3/6) for the ≥70 group, capturing the aggressive tempo of primary motor neuron degeneration. In IDD—which primarily comprised patients in early, clinically stable phases—out-of-boundary rates were 17.0% (8/47) in the 20–49 group and 2.6% (1/38) in the 50–69 group. Age-stratified ROC analysis demonstrated exceptional separation capacity for ALS against healthy controls (area under the curve (AUC): 20–49 years=0.999; 50–69 years=0.964; ≥70 years=0.981) and against IDD (AUC: 20–49 years=0.910; 50–69 years=0.976). Intriguingly, in the 20–49 group where physiological ageing noise was minimal, the platform retained a modest capability to distinguish stable IDD from healthy controls (AUC=0.607).
Conclusion: Age-stratified plasma NfL mapping provides a rigorous normative framework for defining population-specific healthy boundaries in China. Rather than functioning as a standalone differential classifier, the dramatic cross-sectional variance in peripheral NfL magnitude successfully maps the distinct pathological spaces separating primary, continuous neurodegeneration (ALS) from quiescent neuroinflammation (IDD) across the adult lifespan, validating the analytical utility of domestic DiSMS platforms.
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BibTeX
@article{huang2026pathological,
title = {{Pathological separation utility of plasma neurofilament light chain (NfL) detected by a single-molecule immunoassay platform in neurodegenerative diseases}},
author = {Jin Huang and Haiyan Li and Hailan Zhou and Tong Li and Jia Li and Dequan Liu and Keqiang Yan},
journal = {BMJ Neurology Open},
year = {2026},
month = nov,
doi = {10.1136/bmjno-2026-001715},
url = {https://doi.org/10.1136/bmjno-2026-001715},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Pathological separation utility of plasma neurofilament light chain (NfL) detected by a single-molecule immunoassay platform in neurodegenerative diseases
AU - Jin Huang
AU - Haiyan Li
AU - Hailan Zhou
AU - Tong Li
AU - Jia Li
AU - Dequan Liu
AU - Keqiang Yan
PY - 2026
DA - 2026/11/02
JO - BMJ Neurology Open
DO - 10.1136/bmjno-2026-001715
UR - https://doi.org/10.1136/bmjno-2026-001715
AB - Background: To establish age-stratified plasma neurofilament light chain (NfL) reference intervals using a domestic Digital Single-Molecule Sensing (DiSMS) platform and to explore neuropathological profiles across amyotrophic lateral sclerosis (ALS), inflammatory demyelinating diseases (IDD) and healthy individuals. Methods: We enrolled 719 participants (510 healthy controls, 121 ALS, 88 IDD). Age-specific reference intervals defining the healthy boundary were established using the 2.5th–97.5th percentile method. Pathological separation utility was evaluated via age-stratified subgroup comparisons and receiver operating characteristic (ROC) analysis. Results: Plasma NfL levels in healthy individuals increased significantly with age (p<0.0001), with reference intervals of 2.68–17.09 pg/mL (20–49 years), 7.14–61.95 pg/mL (50–69 years) and 14.20–104.71 pg/mL (≥70 years). Out-of-boundary NfL elevation rates demonstrated prominent age-dependent fluctuations. In ALS, out-of-boundary elevation rates were 98.3% (57/58) for the 20–49 age group, 68.4% (39/57) for the 50–69 group and 50.0% (3/6) for the ≥70 group, capturing the aggressive tempo of primary motor neuron degeneration. In IDD—which primarily comprised patients in early, clinically stable phases—out-of-boundary rates were 17.0% (8/47) in the 20–49 group and 2.6% (1/38) in the 50–69 group. Age-stratified ROC analysis demonstrated exceptional separation capacity for ALS against healthy controls (area under the curve (AUC): 20–49 years=0.999; 50–69 years=0.964; ≥70 years=0.981) and against IDD (AUC: 20–49 years=0.910; 50–69 years=0.976). Intriguingly, in the 20–49 group where physiological ageing noise was minimal, the platform retained a modest capability to distinguish stable IDD from healthy controls (AUC=0.607). Conclusion: Age-stratified plasma NfL mapping provides a rigorous normative framework for defining population-specific healthy boundaries in China. Rather than functioning as a standalone differential classifier, the dramatic cross-sectional variance in peripheral NfL magnitude successfully maps the distinct pathological spaces separating primary, continuous neurodegeneration (ALS) from quiescent neuroinflammation (IDD) across the adult lifespan, validating the analytical utility of domestic DiSMS platforms.
SN - 2632-6140
ER -