Levels and Age Dependency of Neurofilament Light and Glial Fibrillary Acidic Protein in Healthy Individuals and Their Relation to the Brain Parenchymal Fraction

Mattias Vågberg; Niklas Norgren; Ann Dring; Thomas Lindqvist; Richard Birgander; Henrik Zetterberg; Anders Svenningsson

doi:10.1371/journal.pone.0135886

Levels and Age Dependency of Neurofilament Light and Glial Fibrillary Acidic Protein in Healthy Individuals and Their Relation to the Brain Parenchymal Fraction

PLoS One. 2015 Aug 28;10(8):e0135886. doi: 10.1371/journal.pone.0135886. eCollection 2015.

Authors

Mattias Vågberg¹, Niklas Norgren², Ann Dring¹, Thomas Lindqvist³, Richard Birgander³, Henrik Zetterberg⁴, Anders Svenningsson¹

Affiliations

¹ Department of Pharmacology and Clinical Neuroscience, Section of Neuroscience, Umeå University, Umeå, Sweden.
² UmanDiagnostics AB, Umeå, Sweden.
³ Department of Radiation Sciences, Section of Diagnostic Radiology, Umeå University, Umeå, Sweden.
⁴ Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology, Queen Square, London, United Kingdom.

Abstract

Background: Neurofilament light (NFL) and Glial Fibrillary Acidic Protein (GFAP) are integral parts of the axonal and astrocytal cytoskeletons respectively and are released into the cerebrospinal fluid (CSF) in cases of cellular damage. In order to interpret the levels of these biomarkers in disease states, knowledge on normal levels in the healthy is required. Another biomarker for neurodegeneration is brain atrophy, commonly measured as brain parenchymal fraction (BPF) using magnetic resonance imaging (MRI). Potential correlations between levels of NFL, GFAP and BPF in healthy individuals have not been investigated.

Objectives: To present levels of NFL and GFAP in healthy individuals stratified for age, and investigate the correlation between them as well as their correlation with BPF.

Methods: The CSF was analysed in 53 healthy volunteers aged 21 to 70 (1 sample missing for GFAP analysis) and 48 of the volunteers underwent determination of BPF using MRI.

Results: Mean (±SD) NFL was 355 ng/L (±214), mean GFAP was 421 ng/L (±129) and mean BPF was 0.867 (±0.035). All three biomarkers correlated with age. NFL also correlated with both GFAP and BPF. When controlled for age, only the correlation between NFL and GFAP retained statistical significance.

Conclusions: This study presents data on age-stratified levels of NFL and GFAP in the CSF of healthy individuals. There is a correlation between levels of NFL and GFAP and both increase with age. A correlation between NFL and BPF was also found, but did not retain statistical significance if controlled for age.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aging / metabolism*
Aging / pathology
Brain / growth & development
Brain / metabolism*
Brain / pathology
Female
Glial Fibrillary Acidic Protein / metabolism*
Humans
Male
Middle Aged
Neurofilament Proteins / metabolism*

Substances

Glial Fibrillary Acidic Protein
Neurofilament Proteins

Grants and funding

The study was partially funded by unrestricted research grants from BiogenIdec AB and Neuro Sweden. Financial support was further provided through a regional agreement between Umeå University and Västerbotten County Council (ALF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. UmanDiagnostics AB provided support in the form of salaries for author NN, supplied NFL-kits for the study and provided lab-space for NFL analysis, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of all authors are articulated in the ‘author contributions’ section.