Plasma and cerebrospinal fluid concentrations of neurofilament light protein correlate in patients with idiopathic normal pressure hydrocephalus

Abstract Background Neurofilament light chain protein (NFL), a marker of neuronal axonal degeneration, is increased in cerebrospinal fluid (CSF) of patients with idiopathic normal pressure hydrocephalus (iNPH). Assays for analysis of NFL in plasma are now widely available but plasma NFL has not been...

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Main Authors: A. Jeppsson, Å. Sandelius, A. Zettergren, S. Kern, I. Skoog, K. Blennow, H. Zetterberg, C. Wikkelsø, P. Hellström, M. Tullberg
Format: Article
Language:English
Published: BMC 2023-07-01
Series:Fluids and Barriers of the CNS
Subjects:
Online Access:https://doi.org/10.1186/s12987-023-00455-y
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author A. Jeppsson
Å. Sandelius
A. Zettergren
S. Kern
I. Skoog
K. Blennow
H. Zetterberg
C. Wikkelsø
P. Hellström
M. Tullberg
author_facet A. Jeppsson
Å. Sandelius
A. Zettergren
S. Kern
I. Skoog
K. Blennow
H. Zetterberg
C. Wikkelsø
P. Hellström
M. Tullberg
author_sort A. Jeppsson
collection DOAJ
description Abstract Background Neurofilament light chain protein (NFL), a marker of neuronal axonal degeneration, is increased in cerebrospinal fluid (CSF) of patients with idiopathic normal pressure hydrocephalus (iNPH). Assays for analysis of NFL in plasma are now widely available but plasma NFL has not been reported in iNPH patients. Our aim was to examine plasma NFL in iNPH patients and to evaluate the correlation between plasma and CSF levels, and whether NFL levels are associated with clinical symptoms and outcome after shunt surgery. Methods Fifty iNPH patients with median age 73 who had their symptoms assessed with the iNPH scale and plasma and CSF NFL sampled pre- and median 9 months post-operatively. CSF plasma was compared with 50 healthy controls (HC) matched for age and gender. Concentrations of NFL were determined in plasma using an in-house Simoa method and in CSF using a commercially available ELISA method. Results Plasma NFL was elevated in patients with iNPH compared to HC (iNPH: 45 (30–64) pg/mL; HC: 33 (26–50) (median; Q1–Q3), p = 0.029). Plasma and CSF NFL concentrations correlated in iNPH patients both pre- and postoperatively (r = 0.67 and 0.72, p < 0.001). We found only weak correlations between plasma or CSF NFL and clinical symptoms and no associations with outcome. A postoperative NFL increase was seen in CSF but not in plasma. Conclusions Plasma NFL is increased in iNPH patients and concentrations correlate with CSF NFL implying that plasma NFL can be used to assess evidence of axonal degeneration in iNPH. This finding opens a window for plasma samples to be used in future studies of other biomarkers in iNPH. NFL is probably not a very useful marker of symptomatology or for prediction of outcome in iNPH.
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spelling doaj.art-b04f5fdf546d4ad4ab16755ac118f9de2023-07-09T11:21:55ZengBMCFluids and Barriers of the CNS2045-81182023-07-012011810.1186/s12987-023-00455-yPlasma and cerebrospinal fluid concentrations of neurofilament light protein correlate in patients with idiopathic normal pressure hydrocephalusA. Jeppsson0Å. Sandelius1A. Zettergren2S. Kern3I. Skoog4K. Blennow5H. Zetterberg6C. Wikkelsø7P. Hellström8M. Tullberg9Hydrocephalus Research Unit, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University HospitalClinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of GothenburgNeuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgNeuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgNeuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgClinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of GothenburgClinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of GothenburgHydrocephalus Research Unit, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University HospitalHydrocephalus Research Unit, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University HospitalHydrocephalus Research Unit, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University HospitalAbstract Background Neurofilament light chain protein (NFL), a marker of neuronal axonal degeneration, is increased in cerebrospinal fluid (CSF) of patients with idiopathic normal pressure hydrocephalus (iNPH). Assays for analysis of NFL in plasma are now widely available but plasma NFL has not been reported in iNPH patients. Our aim was to examine plasma NFL in iNPH patients and to evaluate the correlation between plasma and CSF levels, and whether NFL levels are associated with clinical symptoms and outcome after shunt surgery. Methods Fifty iNPH patients with median age 73 who had their symptoms assessed with the iNPH scale and plasma and CSF NFL sampled pre- and median 9 months post-operatively. CSF plasma was compared with 50 healthy controls (HC) matched for age and gender. Concentrations of NFL were determined in plasma using an in-house Simoa method and in CSF using a commercially available ELISA method. Results Plasma NFL was elevated in patients with iNPH compared to HC (iNPH: 45 (30–64) pg/mL; HC: 33 (26–50) (median; Q1–Q3), p = 0.029). Plasma and CSF NFL concentrations correlated in iNPH patients both pre- and postoperatively (r = 0.67 and 0.72, p < 0.001). We found only weak correlations between plasma or CSF NFL and clinical symptoms and no associations with outcome. A postoperative NFL increase was seen in CSF but not in plasma. Conclusions Plasma NFL is increased in iNPH patients and concentrations correlate with CSF NFL implying that plasma NFL can be used to assess evidence of axonal degeneration in iNPH. This finding opens a window for plasma samples to be used in future studies of other biomarkers in iNPH. NFL is probably not a very useful marker of symptomatology or for prediction of outcome in iNPH.https://doi.org/10.1186/s12987-023-00455-yIdiopathic normal pressure hydrocephalusNeurofilament light chain proteinNFLBiomarkersCSFPlasma
spellingShingle A. Jeppsson
Å. Sandelius
A. Zettergren
S. Kern
I. Skoog
K. Blennow
H. Zetterberg
C. Wikkelsø
P. Hellström
M. Tullberg
Plasma and cerebrospinal fluid concentrations of neurofilament light protein correlate in patients with idiopathic normal pressure hydrocephalus
Fluids and Barriers of the CNS
Idiopathic normal pressure hydrocephalus
Neurofilament light chain protein
NFL
Biomarkers
CSF
Plasma
title Plasma and cerebrospinal fluid concentrations of neurofilament light protein correlate in patients with idiopathic normal pressure hydrocephalus
title_full Plasma and cerebrospinal fluid concentrations of neurofilament light protein correlate in patients with idiopathic normal pressure hydrocephalus
title_fullStr Plasma and cerebrospinal fluid concentrations of neurofilament light protein correlate in patients with idiopathic normal pressure hydrocephalus
title_full_unstemmed Plasma and cerebrospinal fluid concentrations of neurofilament light protein correlate in patients with idiopathic normal pressure hydrocephalus
title_short Plasma and cerebrospinal fluid concentrations of neurofilament light protein correlate in patients with idiopathic normal pressure hydrocephalus
title_sort plasma and cerebrospinal fluid concentrations of neurofilament light protein correlate in patients with idiopathic normal pressure hydrocephalus
topic Idiopathic normal pressure hydrocephalus
Neurofilament light chain protein
NFL
Biomarkers
CSF
Plasma
url https://doi.org/10.1186/s12987-023-00455-y
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