Neurofilament light (NfL) chain levels predict clinical decline in Alzheimer's disease: A systematic review and meta-analysis

作者：Kim S Thomas, Paul Spin, Nikita Sir, Kevin Hou, Nicholas J. Ashton, Henrik Zetterberg, S. K. Miller, Carol Pringle, Richard G. Stefanacci, Claude M. Wischik, Serge Gauthier · 发表于：Journal of Alzheimer s Disease Reports · 年份：2025 · DOI：10.1177/25424823251379878 · 被引用次数：8 · 研究领域：Dementia and Cognitive Impairment Research、Alzheimer's disease research and treatments、Amyotrophic Lateral Sclerosis Research

Background: Regulatory approval of new investigational Alzheimer's disease (AD) therapies could be accelerated if reasonably likely surrogate endpoints could be used. Neurofilament light chain (NfL) has potential utility as a prognostic biomarker of neurodegeneration in AD. Objective: To synthesize available evidence on the relationship between baseline NfL levels and longitudinal clinical decline. Methods: A systematic literature review identified 19 eligible studies, contributing 37 longitudinal statistical models evaluating the association between baseline NfL (plasma or cerebrospinal fluid [CSF]) with subsequent clinical decline based on validated clinical scales including Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale, and Clinical Dementia Rating. Results were pooled via meta-analysis, using partial correlation coefficients (PCC), separately for patient sub-groups (mild cognitive impairment, AD or combined). Results: Across the AD continuum, higher baseline NfL levels were consistently associated with greater cognitive and global clinical decline in most analyses. This pattern was consistent for both plasma (pooled PCC = -0.17 [95% CI = -0.22, -0.12] for MMSE, any AD population) and CSF NfL (pooled PCC = -0.14 [95% CI = -0.24, -0.04] for MMSE, any AD population). The strength of association across multiple clinical endpoints and populations, measured by absolute value of pooled PCC, ranged from 0.13 to 0.25. Conclusions: Th...