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Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study

Journal article
Authors Magnus Gisslén
Richard W. Price
Ulf Andreasson
Niklas Norgren
Staffan Nilsson
Lars Hagberg
Dietmar Fuchs
Serena Spudich
Kaj Blennow
Henrik Zetterberg
Published in EBioMedicine
Volume 3
Pages 135-140
ISSN 2352-3964
Publication year 2016
Published at Department of Mathematical Sciences, Mathematical Statistics
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Institute of Biomedicine, Department of Infectious Medicine
Pages 135-140
Language en
Links dx.doi.org/10.1016/j.ebiom.2015.11....
https://gup.ub.gu.se/file/188423
Keywords Antiretroviral Treatment, Biomarker, Central Nervous System, Cerebrospinal Fluid, CNS, CSF, HAD, HIV, HIV Associated Dementia, Neurofilament Light Chain, NFL, Plasma
Subject categories Neurochemistry, Clinical Medicine

Abstract

Background: Cerebrospinal fluid (CSF) neurofilament light chain protein (NFL) is a sensitive marker of neuronal injury in a variety of neurodegenerative conditions, including the CNS dysfunction injury that is common in untreated HIV infection. However, an important limitation is the requirement for lumbar puncture. For this reason, a sensitive and reliable blood biomarker of CNS injury would represent a welcome advance in both clinical and research settings. Methods: To explore whether plasma concentrations of NFL might be used to detect CNS injury in HIV infection, an ultrasensitive Single molecule array (Simoa) immunoassay was developed. Using a cross-sectional design, we measured NFL in paired CSF and plasma samples from 121 HIV-infected subjects divided into groups according to stage of their systemic disease, presence of overt HIV-associated dementia (HAD), and after antiretroviral treatment (ART)-induced viral suppression. HIV-negative controls were also examined. Findings: Plasma and CSF NFL concentrations were very highly correlated (r=0.89, P<0.0001). While NFL was more than 50-fold lower plasma than CSF it was within the quantifiable range of the new plasma assay in all subjects, including the HIV negatives and the HIV positives with normal CSF NFL concentrations. The pattern of NFL changes were almost identical in plasma and CSF, both exhibiting similar age-related increases in concentrations along with highest values in HAD and substantial elevations in ART-naïve neuroasymptomatic subjects with low blood CD4+ T cells. Interpretation: These results show that plasma NFL may prove a valuable tool to evaluate ongoing CNS injury in HIV infection that may be applied in the clinic and in research settings to assess the presence if active CNS injury. Because CSF NFL is also elevated in a variety of other CNS disorders, sensitive measures of plasma NFL may similarly prove useful in other settings.

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