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

Ou, ZYA; Byrne, LM; Rodrigues, FB; Tortelli, R; Johnson, EB; Foiani, MS; Arridge, M; ... Wild, EJ; + view all (2020) Brain-derived neurotrophic factor in cerebrospinal fluid and plasma is not a biomarker for Huntington's disease. MedRxiv: Cold Spring Harbor, NY, USA. Green open access

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2020 10 medRxiv Brain-derived neurotrophic factor in CSF and plasma is not a biomarker for Huntington's disease.pdf - Accepted Version

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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. 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) were quantified 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. 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.

Type: Working / discussion paper
Title: Brain-derived neurotrophic factor in cerebrospinal fluid and plasma is not a biomarker for Huntington's disease
Open access status: An open access version is available from UCL Discovery
DOI: 10.1101/2020.11.02.20222166
Publisher version: https://doi.org/10.1101/2020.11.02.20222166
Language: English
Additional information: The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license (http://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10114475
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