[Frontiers in Bioscience E4, 950-957, January 1, 2012]

[Frontiers in Bioscience E4, 950-957, January 1, 2012]

Increased levels of hemoglobin and alpha₁-microglobulin in Huntington's disease

Magnus G. Olsson¹, Sara Davidsson¹, Zara Din Muhammad¹, Nayana Lahiri², Sarah J Tabrizi², Bo Akerstrom¹, Maria Bjorkqvist³

1Division of Infection Medicine, Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden, ²Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, England, UK, ³ Neuronal Survival Unit, Department of Experimental Medical Sciences, Wallenberg Neuroscience Center, Lund University, S-221 84 Lund, Sweden

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods: 3.1. Collection and processing of human samples; 3.2. Reagents and proteins; 3.3. Determination of protein carbonyl groups; 3.4. Radioimmunoassay; 3.5. Hemoglobin measurement; 3.6. Thiobarbituric acid-assay; 3.7. Statistical analysis
4. Results: 4.1. Analysis of urine samples in cohort 1; 4.2. Analysis of urine samples in cohort 2; 4.3. Plasma markers of oxidation in cohort 2
5. Discussion
6. Acknowledgments
7. References

1. ABSTRACT

Hemoglobin released from damaged erythrocytes is a major pro-oxidant, generator of free radicals and inflammatory mediator. Huntington's disease is an inherited neurodegenerative disorder characterized by both neurological and systemic abnormalities, in which oxidative stress has been suggested as a possible pathogenic mechanism. In the present work we have investigated levels of hemoglobin and markers of oxidative damage, including the heme- and radical-scavenger alpha₁-microglobulin, in plasma and urine samples from two separate sample cohorts, including controls, premanifest gene carriers and subjects at different stages of Huntington's disease. The results show statistically significant increased levels of hemoglobin and alpha₁-microglobulin in Huntington's disease urine samples. Interestingly, urine hemoglobin levels correlate with clinical severity. The results suggest that hemolysis may be linked to the pathogenesis of Huntington's disease and that assay of hemoglobin and alpha₁-microglobulin may provide biomarkers that are linked to biologically relevant processes.