Role of Neurofilament Light Chain as a Potential Biomarker for Alzheimer's Disease: A Correlative Meta-Analysis

Abstract

Neurofilament light (NFL) is a putative biomarker of neurodegeneration. This study evaluates the correlative association of NFL with Alzheimer's disease (AD) indices. Relevant studies were identified after a literature search in electronic databases and study selection was based on pre-determined eligibility criteria. Correlation coefficients between NFL levels and important AD indices reported by individual studies were pooled as z-scores. Meta-regression analyses were performed to evaluate the relationships between important covariates. Data from 38 studies (age 68.3 years [95% confidence interval (CI): 65.7, 70.9]; 54 % [95% CI: 50, 57] females) were used. Meta-analyses of correlation coefficients reported by the included studies showed that NFL levels in blood and cerebrospinal fluid (CSF) correlated well (r = 0.59 [95% CI: 0.45, 0.71]; p < 0.0001). NFL levels correlated with MMSE score (r = -0.345 [95% CI: -0.43, -0.25]; p = 0.0001), and age (r = 0.485 [95% CI: 0.35, 0.61]; p = 0.00001). CSF NFL levels correlated with total tau (t-tau; r = 0.39 [95% CI: 0.27, 0.50]; p = 0.0001), phosphorylated tau (p-tau; r = 0.34 [95% CI: 0.19, 0.47]; p = 0.00001), and neurogranin (r = 0.25 [95% CI: 0.12, 0.37]; p = 0.001) but not with beta amyloid (Aβ) (r = 0.00 [95%CI: -0.13, 0.12]; p = 0.937). In meta-regression, MMSE scores were associated inversely with blood NFL (metaregression coefficient (MC) -0.236 [95% CI:-0.40, -0.072; p = 0.008), and age (MC) -0.235 [-0.36, -0.11]; p = 0.001) and positively with CSF Aβ-42 (MC 0.017 [0.010, 0.023]; p = 0.00001). NFL has good correlations with t-tau, and p-tau in CSF and CSF NFL levels correlates well with blood NFL levels. These results show that NFL can be a useful biomarker for improving diagnosis and predicting prognosis in AD patients especially if age weighted.

Keywords: Alzheimer's disease; biomarker; correlation; diagnosis; neurofilament light.

Figure 1

A flowchart of study screening and selection process.

Figure 2

Forest graphs showing the meta-analyses of correlation coefficients (converted to z-scores) between NFL levels and MMSE (min-mental state examination) score, age, and EYO (estimated year of onset).

Figure 3

Forest graphs showing the meta-analyses of correlation coefficients (converted to z-scores) between NFL levels and biomarkers of AD. p-tau, phosphorylated tau, t-tau, total tau; YLK-40, and Chitinase-3-like protein 1.

Figure 4

Meta-regression scatterplots showing the relationships between MMSE score and (A) NFL levels in CSF and (B) NFL levels in blood.

Figure 5

Meta-regression scatterplots showing the relationships between MMSE score and (A) beta-amyloid-42, and (B) age.

Figure 6

A forest graph showing the changes in NFL levels through time in AD patients.