Neurofilament light chain in Alzheimer's disease

Abstract

Neurofilament light chain (NfL) is a sensitive marker of neuroaxonal injury with growing clinical relevance in Alzheimer's disease (AD). Across cohorts, blood and CSF NfL concentrations are higher in AD than controls, with reported 1.7-1.8-fold elevations and a plasma-CSF correlation of r = 0.78, supporting measurement interchangeability for clinical use. Longitudinal data show that presymptomatic converters exhibit ≈20 % higher serum NfL and that baseline levels predict progression with ≈80 % accuracy, highlighting value for risk stratification. In prodromal and dementia-stage AD, higher baseline NfL tracks faster worsening on MMSE/CDR and greater brain atrophy, with typical longitudinal correlations r = 0.6-0.8. CSF rises often precede plasma by several months, but trajectories are parallel, enabling minimally invasive monitoring. For detection, NfL discriminates dementia from controls with AUCs frequently >0.95, although NfL alone is not AD-specific; pairing with other markers improves differential diagnosis, with a total-tau/NfL ratio achieving AUC≈0.95 for early AD versus FTD. Reported plasma decision thresholds vary by assay and cohort (≈18-34 pg/mL), underscoring the need for platform-specific calibration and age/stage adjustment. Overall, quantitative evidence supports NfL as a robust diagnostic and prognostic biomarker for AD, suitable for monitoring and trial enrichment; explicit reporting of fold-changes, AUCs, and correlations will improve interpretability and facilitate adoption in clinical and research applications.

Keywords: Alzheimer’s disease; Biomarker; Blood-based diagnostics; Cerebrospinal fluid (CSF); Neurofilament light chain (NfL); Single molecule array.