Background No candidate blood, CSF or urine biomarkers for HD have been clinically validated. 8-hydroxy-deoxy-guanosine (8OHdG) has been proposed as a candidate biomarker. Increased levels of 8OHdG have been reported in post-mortem brains1 2 and in serum,3 leucocytes4 and plasma5 of HD patients. All of the published studies on 8OHdG utilised a liquid chromatography electrochemical array (LCECA) assay.
Aims To evaluate the potential of plasma 8-OHdG as a biomarker of HD state or progression and to develop a general set of procedures to test potential biomarkers.
Methods We established a new liquid chromatography-mass spectrometry (LCMS) assay for 8OHdG and used it to measure 8OHdG levels in a cross-sectional plasma collection from the PREDICT-HD study. Next, longitudinal plasma samples taken 24 months apart from 160 TRACK-HD subjects, along with control plasma with added (“spiked”) 8OHdG, were sent blindly to two laboratories for measurement of 8OHdG using either the LCECA or the LCMS assay.
Results We found no differences in 8OHdG levels between controls, premanifest HD and clinically diagnosed HD subjects from the PREDICT-HD study using the LCMS assay. A blinded head to head comparison showed the LCMS assay to be more accurate than the LCECA assay at measuring 8OHdG from spiked control plasma. Both assays were consistent in demonstrating no cross sectional differences in plasma 8OHdG between TRACK-HD controls, premanifest HD and early symptomatic HD subjects, and no longitudinal changes in any of the disease groups over 24 month.
Conclusions Plasma concentration of 8-OHdG should not be considered a potential biomarker of disease state or disease progression in HD. To avoid the errors that have plagued such analyses, studies of all putative biomarkers should employ (1) blinded sample analyses; (2) verification of measurements by independent analytic methods; (3) standard curves; and (4) collection and storage of biological fluids under strict quality control.
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