The association between retinal neurodegeneration and plasma neurofilament light chain: A population‐based study

Abstract

AbstractBackgroundBoth plasma neurofilament light chain (NfL) levels and retinal layer volumes have emerged as biomarkers of central neurodegeneration, the former highlighting neuroaxonal damage, the latter as an extension of the brain susceptible to similar injuries. To date, the extent to which plasma NfL levels and retinal layer volumes could be used as complementary biomarkers of brain health is unknown. Therefore, we assessed their association in the general populationMethodThe study is based on the first 5000 participants of the Rhineland Study, a population‐based cohort study in people aged 30 years and above in Bonn (Germany). We included all participants with complete spectral‐domain optic coherence tomography (SD‐OCT) and plasma NfL data (N=4396, after removal of three outliers due to extreme values). We applied multivariable regression analysis to investigate associations between different retinal layer volumes and plasma NfL levels, assessing effect modification by age, sex, hypertension, smoking and presence of neurological diseases (N=95, including stroke, dementia and multiple sclerosis).ResultNfL levels increased, while ganglion cell layer (GCL) volume decreased exponentially with advancing age. Among the different retinal layers, GCL volume was most closely associated with NfL levels, with a strong age‐dependent association: while no association was evident in young individuals, in older individuals lower GCL volume was related to higher NfL levels (std. beta for the interaction effect of GCL with highest tertile of age = ‐0.032, 95% CI [‐0.06 ‐ ‐0.005],p=0.02). Similarly, smaller GCL volume was associated with higher NfL levels in participants with hypertension (std.beta ‐0.06, 95% CI [‐0.011 ‐ ‐0.02],p=0.003) or a neurological disease (std. beta ‐0.018, 95%CI [‐0.035 ‐ ‐0.001], p=0.037), but not in those without disease.ConclusionOur findings indicate that retinal layers volume,in particular GCL, more closely reflect neuroaxonal damage in higher age or in the presence of cardiovascular risk factors and neurological diseases.