title: Cerebrospinal fluid total tau concentration predicts clinical phenotype in Huntington's disease.
abstract: Huntington's disease (HD) is a hereditary neurodegenerative condition with no therapeutic intervention known to alter disease progression, but several trials are ongoing and biomarkers of disease progression are needed. Tau is an axonal protein, often altered in neurodegeneration, and recent studies pointed out its role on HD neuropathology. Our goal was to study whether cerebrospinal fluid (CSF) tau is a biomarker of disease progression in HD. After informed consent, healthy controls, pre-symptomatic and symptomatic gene expansion carriers were recruited from two HD clinics. All participants underwent assessment with the Unified HD Rating Scale '99 (UHDRS). CSF was obtained according to a standardized lumbar puncture protocol. CSF tau was quantified using enzyme-linked immunosorbent assay. Comparisons between two groups were tested using ancova. Pearson's correlation coefficients were calculated for disease progression. Significance level was defined as p < 0.05. Seventy-six participants were included in this cross-sectional multicenter international pilot study. Age-adjusted CSF tau was significantly elevated in gene expansion carriers compared with healthy controls (p = 0.002). UHDRS total functional capacity was significantly correlated with CSF tau (r = -0.29, p = 0.004) after adjustment for age, and UHDRS total motor score was significantly correlated with CSF tau after adjustment for age (r = 0.32, p = 0.002). Several UHDRS cognitive tasks were also significantly correlated with CST total tau after age-adjustment. This study confirms that CSF tau concentrations in HD gene mutation carriers are increased compared with healthy controls and reports for the first time that CSF tau concentration is associated with phenotypic variability in HD. These conclusions strengthen the case for CSF tau as a biomarker in HD. In the era of novel targeted approaches to Huntington's disease, reliable biomarkers are needed. We quantified Tau protein, a marker of neuronal death, in cerebrospinal fluid and found it was increased in patients with Huntington's disease and predicted motor, cognitive, and functional disability in patients. It is therefore likely to be a biomarker of disease progression, and possibly of therapeutic response. Read the Editorial Highlight for this article on page 9.
authors.affiliation: Huntington's Disease Centre, Institute of Neurology, University College London, London, UK.
authors.forename: Filipe Brogueira
authors.initials: FB
authors.lastname: Rodrigues
authors.affiliation: Huntington's Disease Centre, Institute of Neurology, University College London, London, UK.
authors.forename: Lauren
authors.initials: L
authors.lastname: Byrne
authors.affiliation: Huntington's Disease Centre, Institute of Neurology, University College London, London, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: McColgan
authors.affiliation: Huntington's Disease Centre, Institute of Neurology, University College London, London, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Robertson
authors.affiliation: Huntington's Disease Centre, Institute of Neurology, University College London, London, UK.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Tabrizi
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Blair R
authors.initials: BR
authors.lastname: Leavitt
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.|Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Huntington's Disease Centre, Institute of Neurology, University College London, London, UK. e.wild@ucl.ac.uk.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Wild
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003430:Cross-Sectional Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006579:Heterozygote; D006801:Humans; D006816:Huntington Disease / Q000134:cerebrospinal fluid* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010865:Pilot Projects; D011237:Predictive Value of Tests; D055815:Young Adult; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; D016875:tau Proteins
keywords: Huntington disease; biomarkers; cerebrospinal fluid; pilot projects; tau proteins