title: Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address: magnus.gisslen@gu.se.
authors: Magnus
authors: M
authors: Gisslén
authors: Department of Neurology, University of California San Francisco, USA.
authors: Richard W
authors: RW
authors: Price
authors: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
authors: Ulf
authors: U
authors: Andreasson
authors: UmanDiagnostics, Umeå, Sweden.
authors: Niklas
authors: N
authors: Norgren
authors: Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden.
authors: Staffan
authors: S
authors: Nilsson
authors: Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Lars
authors: L
authors: Hagberg
authors: Division of Biological Chemistry, Innsbruck Medical University, Innsbruck, Austria.
authors: Dietmar
authors: D
authors: Fuchs
authors: Department of Neurology, Yale University School of Medicine, New Haven, USA.
authors: Serena
authors: S
authors: Spudich
authors: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
authors: Kaj
authors: K
authors: Blennow
authors: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology, Queen Square, London, United Kingdom.
authors: Henrik
authors: H
authors: Zetterberg
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D020805:Central Nervous System Viral Diseases / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000097:blood* / Q000134:cerebrospinal fluid; D012680:Sensitivity and Specificity; D019562:Viral Load
chemical_list: D015415:Biomarkers; D016900:Neurofilament Proteins; C044882:neurofilament protein L
keywords: Antiretroviral Treatment; Biomarker; CNS; CSF; Central Nervous System; Cerebrospinal Fluid; HAD; HIV; HIV Associated Dementia; NFL; Neurofilament Light Chain; Plasma