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

Abstract 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...

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Autores principales:	Zhen-Yi Andy Ou, Lauren M. Byrne, Filipe B. Rodrigues, Rosanna Tortelli, Eileanoir B. Johnson, Martha S. Foiani, Marzena Arridge, Enrico De Vita, Rachael I. Scahill, Amanda Heslegrave, Henrik Zetterberg, Edward J. Wild
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/87c1ce7916eb411a90ed61e22ac22bba
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spelling	oai:doaj.org-article:87c1ce7916eb411a90ed61e22ac22bba2021-12-02T14:26:54ZBrain-derived neurotrophic factor in cerebrospinal fluid and plasma is not a biomarker for Huntington’s disease10.1038/s41598-021-83000-x2045-2322https://doaj.org/article/87c1ce7916eb411a90ed61e22ac22bba2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83000-xhttps://doaj.org/toc/2045-2322Abstract 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.Zhen-Yi Andy OuLauren M. ByrneFilipe B. RodriguesRosanna TortelliEileanoir B. JohnsonMartha S. FoianiMarzena ArridgeEnrico De VitaRachael I. ScahillAmanda HeslegraveHenrik ZetterbergEdward J. WildNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zhen-Yi Andy Ou Lauren M. Byrne Filipe B. Rodrigues Rosanna Tortelli Eileanoir B. Johnson Martha S. Foiani Marzena Arridge Enrico De Vita Rachael I. Scahill Amanda Heslegrave Henrik Zetterberg Edward J. Wild Brain-derived neurotrophic factor in cerebrospinal fluid and plasma is not a biomarker for Huntington’s disease
description	Abstract 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	article
author	Zhen-Yi Andy Ou Lauren M. Byrne Filipe B. Rodrigues Rosanna Tortelli Eileanoir B. Johnson Martha S. Foiani Marzena Arridge Enrico De Vita Rachael I. Scahill Amanda Heslegrave Henrik Zetterberg Edward J. Wild
author_facet	Zhen-Yi Andy Ou Lauren M. Byrne Filipe B. Rodrigues Rosanna Tortelli Eileanoir B. Johnson Martha S. Foiani Marzena Arridge Enrico De Vita Rachael I. Scahill Amanda Heslegrave Henrik Zetterberg Edward J. Wild
author_sort	Zhen-Yi Andy Ou
title	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_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_sort	brain-derived neurotrophic factor in cerebrospinal fluid and plasma is not a biomarker for huntington’s disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/87c1ce7916eb411a90ed61e22ac22bba
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Brain-derived neurotrophic factor in cerebrospinal fluid and plasma is not a biomarker for Huntington’s disease

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