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

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

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.

Original languageEnglish
Article number3481
JournalScientific Reports
Volume11
Issue number1
DOIs
Publication statusPublished - Dec 2021

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