Abstract
J Alzheimers Dis Rep. 2025 Sep 22;9:25424823251379878. doi: 10.1177/25424823251379878. eCollection 2025 Jan-Dec.
ABSTRACT
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: The results support the utility of NfL as a predictive biomarker for progression of clinical decline in AD patients.
PMID:41000329 | PMC:PMC12457754 | DOI:10.1177/25424823251379878
UK DRI Authors
