Abstract

Blood Neurofilament light chain (NfL) has been suggested as a promising biomarker in several neurological conditions. Since blood NfL is the consequence of leaked NfL from the cerebrospinal fluid, differences in individuals’ Body Mass Index (BMI) or blood volume (BV) might affect its correlation to other biomarkers and disease outcomes. Here, we investigated the correlation between plasma NfL, BMI, and BV in 662 controls and 2,586 multiple sclerosis cases. We found a significant negative correlation between plasma NfL, BMI/BV in both groups. Our results highlight the potential confounding effect of BMI/BV on associations between blood NfL and disease outcomes.

Highlights

  • Neurofilament light chain (NfL) proteins are part of the neuronal structure supporting the radial growth of axons and maintaining their size, shape, and caliber

  • Serum and plasma NfL measures have been used as a biomarker of disease activity and treatment response in multiple sclerosis[3]; to what degree differences in individuals’ blood volume (BV) and body mass index (BMI) might affect the correlation between blood and cerebrospinal fluid (CSF) concentrations of NfL has not been investigated

  • Plasma NfL decreased by 0.02 in cases and À0.02 pg/mL (95%CI: À0.03 to À0.01, P < 0.001) per unit of BMI in controls

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Summary

Introduction

Neurofilament light chain (NfL) proteins are part of the neuronal structure supporting the radial growth of axons and maintaining their size, shape, and caliber. Larger myelinated axons abundantly express NfL even in healthy individuals in an age-dependent manner. Increased NfL levels in cases compared to age-matched controls are present in the cerebrospinal fluid (CSF) across a range of conditions characterized by neuronal and axonal degeneration including multiple sclerosis, Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, HIV-associated dementia, etc.[1,2] The recently developed single molecule array can detect very low concentrations of leaked NfL (pg/mL) from CSF in blood. Serum and plasma NfL measures have been used as a biomarker of disease activity and treatment response in multiple sclerosis[3]; to what degree differences in individuals’ blood volume (BV) and body mass index (BMI) might affect the correlation between blood and CSF concentrations of NfL has not been investigated

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