Cargando…

Brain-derived neurotrophic factor in cerebrospinal fluid and plasma is not a biomarker for Huntington’s disease

Brain-derived neurotrophic factor (BDNF) is implicated in the survival of striatal neurons. BDNF function is reduced in Huntington’s disease (HD), possibly because mutant huntingtin impairs its cortico-striatal transport, contributing to striatal neurodegeneration. The BDNF trophic pathway is a ther...

Descripción completa

Detalles Bibliográficos
Autores principales: Ou, Zhen-Yi Andy, Byrne, Lauren M., Rodrigues, Filipe B., Tortelli, Rosanna, Johnson, Eileanoir B., Foiani, Martha S., Arridge, Marzena, De Vita, Enrico, Scahill, Rachael I., Heslegrave, Amanda, Zetterberg, Henrik, Wild, Edward J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876124/
https://www.ncbi.nlm.nih.gov/pubmed/33568689
http://dx.doi.org/10.1038/s41598-021-83000-x
_version_ 1783649913711624192
author Ou, Zhen-Yi Andy
Byrne, Lauren M.
Rodrigues, Filipe B.
Tortelli, Rosanna
Johnson, Eileanoir B.
Foiani, Martha S.
Arridge, Marzena
De Vita, Enrico
Scahill, Rachael I.
Heslegrave, Amanda
Zetterberg, Henrik
Wild, Edward J.
author_facet Ou, Zhen-Yi Andy
Byrne, Lauren M.
Rodrigues, Filipe B.
Tortelli, Rosanna
Johnson, Eileanoir B.
Foiani, Martha S.
Arridge, Marzena
De Vita, Enrico
Scahill, Rachael I.
Heslegrave, Amanda
Zetterberg, Henrik
Wild, Edward J.
author_sort Ou, Zhen-Yi Andy
collection PubMed
description Brain-derived neurotrophic factor (BDNF) is implicated in the survival of striatal neurons. BDNF function is reduced in Huntington’s disease (HD), possibly because mutant huntingtin impairs its cortico-striatal transport, contributing to striatal neurodegeneration. The BDNF trophic pathway is a therapeutic target, and blood BDNF has been suggested as a potential biomarker for HD, but BDNF has not been quantified in cerebrospinal fluid (CSF) in HD. We quantified BDNF in CSF and plasma in the HD-CSF cohort (20 pre-manifest and 40 manifest HD mutation carriers and 20 age and gender-matched controls) using conventional ELISAs and an ultra-sensitive immunoassay. BDNF concentration was below the limit of detection of the conventional ELISAs, raising doubt about previous CSF reports in neurodegeneration. Using the ultra-sensitive method, BDNF concentration was quantifiable in all samples but did not differ between controls and HD mutation carriers in CSF or plasma, was not associated with clinical scores or MRI brain volumetric measures, and had poor ability to discriminate controls from HD mutation carriers, and premanifest from manifest HD. We conclude that BDNF in CSF and plasma is unlikely to be a biomarker of HD progression and urge caution in interpreting studies where conventional ELISA was used to quantify CSF BDNF.
format Online
Article
Text
id pubmed-7876124
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-78761242021-02-11 Brain-derived neurotrophic factor in cerebrospinal fluid and plasma is not a biomarker for Huntington’s disease Ou, Zhen-Yi Andy Byrne, Lauren M. Rodrigues, Filipe B. Tortelli, Rosanna Johnson, Eileanoir B. Foiani, Martha S. Arridge, Marzena De Vita, Enrico Scahill, Rachael I. Heslegrave, Amanda Zetterberg, Henrik Wild, Edward J. Sci Rep Article Brain-derived neurotrophic factor (BDNF) is implicated in the survival of striatal neurons. BDNF function is reduced in Huntington’s disease (HD), possibly because mutant huntingtin impairs its cortico-striatal transport, contributing to striatal neurodegeneration. The BDNF trophic pathway is a therapeutic target, and blood BDNF has been suggested as a potential biomarker for HD, but BDNF has not been quantified in cerebrospinal fluid (CSF) in HD. We quantified BDNF in CSF and plasma in the HD-CSF cohort (20 pre-manifest and 40 manifest HD mutation carriers and 20 age and gender-matched controls) using conventional ELISAs and an ultra-sensitive immunoassay. BDNF concentration was below the limit of detection of the conventional ELISAs, raising doubt about previous CSF reports in neurodegeneration. Using the ultra-sensitive method, BDNF concentration was quantifiable in all samples but did not differ between controls and HD mutation carriers in CSF or plasma, was not associated with clinical scores or MRI brain volumetric measures, and had poor ability to discriminate controls from HD mutation carriers, and premanifest from manifest HD. We conclude that BDNF in CSF and plasma is unlikely to be a biomarker of HD progression and urge caution in interpreting studies where conventional ELISA was used to quantify CSF BDNF. Nature Publishing Group UK 2021-02-10 /pmc/articles/PMC7876124/ /pubmed/33568689 http://dx.doi.org/10.1038/s41598-021-83000-x Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ou, Zhen-Yi Andy
Byrne, Lauren M.
Rodrigues, Filipe B.
Tortelli, Rosanna
Johnson, Eileanoir B.
Foiani, Martha S.
Arridge, Marzena
De Vita, Enrico
Scahill, Rachael I.
Heslegrave, Amanda
Zetterberg, Henrik
Wild, Edward J.
Brain-derived neurotrophic factor in cerebrospinal fluid and plasma is not a biomarker for Huntington’s disease
title Brain-derived neurotrophic factor in cerebrospinal fluid and plasma is not a biomarker for Huntington’s disease
title_full Brain-derived neurotrophic factor in cerebrospinal fluid and plasma is not a biomarker for Huntington’s disease
title_fullStr Brain-derived neurotrophic factor in cerebrospinal fluid and plasma is not a biomarker for Huntington’s disease
title_full_unstemmed Brain-derived neurotrophic factor in cerebrospinal fluid and plasma is not a biomarker for Huntington’s disease
title_short Brain-derived neurotrophic factor in cerebrospinal fluid and plasma is not a biomarker for Huntington’s disease
title_sort brain-derived neurotrophic factor in cerebrospinal fluid and plasma is not a biomarker for huntington’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876124/
https://www.ncbi.nlm.nih.gov/pubmed/33568689
http://dx.doi.org/10.1038/s41598-021-83000-x
work_keys_str_mv AT ouzhenyiandy brainderivedneurotrophicfactorincerebrospinalfluidandplasmaisnotabiomarkerforhuntingtonsdisease
AT byrnelaurenm brainderivedneurotrophicfactorincerebrospinalfluidandplasmaisnotabiomarkerforhuntingtonsdisease
AT rodriguesfilipeb brainderivedneurotrophicfactorincerebrospinalfluidandplasmaisnotabiomarkerforhuntingtonsdisease
AT tortellirosanna brainderivedneurotrophicfactorincerebrospinalfluidandplasmaisnotabiomarkerforhuntingtonsdisease
AT johnsoneileanoirb brainderivedneurotrophicfactorincerebrospinalfluidandplasmaisnotabiomarkerforhuntingtonsdisease
AT foianimarthas brainderivedneurotrophicfactorincerebrospinalfluidandplasmaisnotabiomarkerforhuntingtonsdisease
AT arridgemarzena brainderivedneurotrophicfactorincerebrospinalfluidandplasmaisnotabiomarkerforhuntingtonsdisease
AT devitaenrico brainderivedneurotrophicfactorincerebrospinalfluidandplasmaisnotabiomarkerforhuntingtonsdisease
AT scahillrachaeli brainderivedneurotrophicfactorincerebrospinalfluidandplasmaisnotabiomarkerforhuntingtonsdisease
AT heslegraveamanda brainderivedneurotrophicfactorincerebrospinalfluidandplasmaisnotabiomarkerforhuntingtonsdisease
AT zetterberghenrik brainderivedneurotrophicfactorincerebrospinalfluidandplasmaisnotabiomarkerforhuntingtonsdisease
AT wildedwardj brainderivedneurotrophicfactorincerebrospinalfluidandplasmaisnotabiomarkerforhuntingtonsdisease