8OHdG as a marker for Huntington disease progression

David Craufurd, Jeffrey D. Long, Wayne R. Matson, Andrew R. Juhl, Blair R. Leavitt, Jane S. Paulsen

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Leukocyte 8-hydroxydeoxyguanosine (8OHdG) is an indicator of oxidative stress, impaired metabolism, and mitochondrial dysfunction, features that have been implicated in Huntington disease (HD). Increased levels of 8OHdG have been reported in the caudate, parietal cortex, and peripherally in the serum and leukocytes, in patients diagnosed with HD. However, little is known about levels in prodromal patients and changes that might occur as the disease progresses. To address these issues, 8OHdG was tracked over time for a subset of participants enrolled in the PREDICT-HD study. Participants were stratified into four groups based on proximity to HD diagnosis at study entry: Controls (gene-negative individuals), Low (low probability of near-future diagnosis), Medium, and High. Blood samples were analyzed using Liquid Chromatography Electrochemical Array, and for comparison purposes, a separate cross-sectional sample was analyzed using liquid chromatography coupled with multiple-reaction-monitoring mass spectrometry. Longitudinal data analysis showed that initial status (at study entry) and annual rate of change varied as a function of proximity group, adjusting for sex, education, age at study entry, and site effects. Overall levels were lowest for the Control group and highest for the High group, and the rate of increase varied in a similar manner. The finding that 8OHdG concentrations increased as a function of proximity to projected disease diagnosis and duration indicates support for the continued assessment of 8OHdG as a robust clinical HD biomarker. © 2012 Elsevier Inc.
    Original languageEnglish
    Pages (from-to)625-634
    Number of pages9
    JournalNeurobiology of disease
    Volume46
    Issue number3
    DOIs
    Publication statusPublished - Jun 2012

    Keywords

    • 8OHdG
    • Biomarker
    • Huntington disease
    • Mitochondrial dysfunction
    • Oxidative stress
    • PREDICT-HD

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