Plasma Neurofilament Light Chain May Be a Biomarker for the Inverse Association Between Cancers and Neurodegenerative Diseases.

Shunjie Liu,Junhao Pan,Zhenze Huang,Lijin Zhang,Zhong Li,Qingfeng Lei,Yangyang Meng

doi:10.3389/fnagi.2020.00010

Abstract

An inverse association may exist between cancers and neurodegenerative diseases, although convenient biomarkers for verifying this inverse association are lacking. Plasma neurofilament light chain (NfL) is a novel biomarker for neurodegenerative diseases, such as Alzheimer’s disease (AD), but it has not been measured in patients with cancers, such as gastric cancer (GC). We aimed to explore whether plasma NfL could be a biomarker for GC and AD and whether an inverse association of NfL exists between GC and AD. In this study, plasma NfL levels of 60 normal controls (NC), 91 GC subjects, and 74 AD subjects were measured by a highly sensitive single-molecule array assay. We found that GC subjects expressed lower plasma NfL levels but AD subjects expressed higher plasma NfL levels than NCs. After controlling for confounding factors, plasma NfL levels in the GC group were associated with serum tumor marker levels, and plasma NfL levels in the AD group were associated with cognitive performance and cerebrospinal fluid (CSF) pathological marker levels. Across the entire cohort, plasma NfL levels were associated with cognitive performance, CSF pathological marker levels and serum tumor marker levels. These results suggest thatplasma NfL may be a potential biomarker for GC and AD and may be convenient for evaluating the inverse association between cancers and neurodegenerative diseases.

Highlights

With the agingworldwide population, the prevalence of cancers and neurodegenerative diseases is rapidly rising (Wimo et al, 2013; Bray et al, 2018)
Significant differences were observed in Mini-Mental State Examination (MMSE) scores, Montreal Cognitive Assessment (MoCA) scores, Aβ1−42levels, t-tau levels,p-tau181levels, CEAlevels, carbohydrate antigen (CA) 19-9levels, and CA 125 levels.Post hoc tests indicated that Alzheimer’s disease (AD) subjects had lower MMSE scores, MoCA scores and Aβ1−42levels and higher t-tau levels andp-tau181levels than gastric cancer (GC) subjects and normal controls (NC), with no differences between GC subjects and NCs
Plasma neurofilament light chain (NfL) levels were negatively correlated with MMSE and MoCA scores within the AD group

Summary

Introduction

The prevalence of cancers and neurodegenerative diseases is rapidly rising (Wimo et al, 2013; Bray et al, 2018). These two types of diseases have both become key focuses of research because oftheir high mortality rate and lack of efficient treatments at the highly progressed stage. An inverse association may exist between cancers and chronic neurodegenerative diseases. There is still a lack of objective and convenient biomarkers to verify this potential inverse association

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