Huntington’ disease – imbalance of amino acid levels in plasma of patients and mutation carriers
More details
Hide details
Department of Biochemistry and Biopharmaceuticals, National Medicines Institute, Warsaw, Poland
Department of Social Medicine, Poznan University of Medical Sciences, Poland
Ann Agric Environ Med. 2013;20(4):779–783
Determination of the plasma amino acid (AA) levels in Huntington’s disease (HD) can make it possible to find the metabolic markers used in early diagnosis. The aim of the presented study was to determine the AA profile in plasma samples from HD patients and presymptomatic carriers, compared to healthy subjects. The AA profile was analyzed with HPLC. The study concerned 59 participants: 30 subjects with abnormal CAG repeats expansion (>36) in the HTT gene, and 29 healthy subjects. Each participant was analyzed with regard to the parameters characterizing the metabolic state and protein metabolism, such as: urea, creatinine, glucose, total protein, TSH (thyroid-stimulating hormone), cortisol, ESR (erythrocyte sedimentation rate), and CRP (C-reactive protein). Simple statistical comparisons showed 5 AA to be significantly lower in the HD group, compared to the control group, i.e.: Asn, His, Leu, Ser, Thr. Creatinine and creatinine clirens were found to be lower in the HD group, compared to controls, while ESR was noticed to be higher. As a result of Canonical Discriminant Analysis, 5 of all AA assayed (Leu, Gln, Asn, Ser and Lys) were selected as variables that allow distinguishing between HD patients and healthy subjects with 75% of correctness. Concerning AA profile and biochemical markers, Canonical Discriminant Analysis detected a panel of variables (Ser, Asn, Gln, Orn, Pro, Arg, Met, Cit, Val, TSH, glucose, urea, creatinine clirens, total protein, cortisol, CRP) distinguishing HD from the control group, with 90% of correctness. Among all the parameters tested, Asn and Ser were revealed in all statistical analyses and could be considered as potential plasma HD biomarkers.
Mochel F, Charles P, Seguin F, Barritault J, Coussieu Ch, Perin L et al. Early energy deficit in Huntington disease: Identification of a plasma biomarker traceable during disease progression. PLoS ONE 2007; 2:e647. doi: 10.1371/journal.pone.0000647.
Handley O J, van Walsem M, Juni P, Bachoud-Levi A-C, Bentivoglio AR, Bonelli RM, et al. Study Protocol of Registry -version 2.0 – European Huntington´s Disease Network (EHDN). Hygeia Public Health 2011; 46: 115–182.
Jaworska M, Stańczyk M, Kłaczkow G, Wilk M, Anuszewska E, Barzał J, et al. New approach for amino acid profiling in human plasma by selective fluorescence derivatization. Amino Acids 2012; 43(4): 1653–1661.
Le Boucher J, Charret C, Coudray-Lucas C, Giboudeau J, Cynober L. Amino acid determination in biological fluids by automated ionexchange chromatography: performance of Hitachi L-8500A. Clin Chem. 1997; 43: 1421–1428.
van der Burg JMM, Bacos K, Wood NI, Lidquist A, Wierup N, Woodman B et al. Increased metabolism in the R6/2 mouse model of Huntington’s disease. Neurobiol Dis. 2008; 29: 41–51.
Weir DW, Sturrock A, Leavitt BR. Development of biomarkers for Huntington’s disease. Lancet Neurol. 2011; 10: 573–590.
Stoy N, Mackay GM, Forrest CM, Christofides J, Egerton M, Stone TW, et al. Tryptophan metabolism and oxidative stress in patients with Huntington’s disease. J Neurochem. 2005; 93: 611–623.
Mochel F, Benaich S, Rabier D, Durr A. Validation of plasma branched chain amino acids as biomarkers in Huntington disease. Arch Neurol. 2011; 68: 265–267.
Reilmann R, Rolf LH, Lange HW. Decreased plasma alanine and isoleucine in Huntington’s disease. Acta Neurol Scand. 1995; 91: 222–224.
Kuiper MA, Teerlink T, Visser JJ, Bergmans PL, Scheltens P, Wolters EC. L-glutamate, L-arginine and L-citrulline levels in cerebrospinal fluid of Parkinson’s disease, multiple system atrophy, and Alzheimer’s disease patients. J Neural Transm. 2000; 107: 183–189.
Oepen G, Cramer H, Bernasconi R, Martin P. Huntington’s disease – imbalance of free amino acids in the cerebrospinal fluid of patients and offspring at-risk. Arch Psychiat Nervenkrankh. 1982; 231: 131–140.
Moffett JR, Ross B, Arun P, Madhavarao ChN, Namboodiri AMA. N-Acetylaspartate in the CNS: from neurodiagnostics to neurobiology. Prog Neurobiol. 2007; 81: 89–131.
Jenkins BG, Klivenyi P, Kustermann E, Andreassen OA, Ferrante RJ, Rosen BR et al. Nonlinear decrease over time in N-acetyl aspartate levels in the absence of neuronal loss and increases in glutamine and glucose in transgenic Huntington’s disease mice. J Neurochem. 2000; 74: 2108–2019.
Shimizu T, Matsuoka Y, Shirasawa T. Biological significance of isoaspartate and its repair system. Biol Pharm Bull. 2005; 28: 1590–1596.
Yamamoto T, Nishizaki I, Furuya S, Hirabayashi Y, Takahashi K, Okuyama S et al. Characterization of rapid and high-affinity uptake of L-serine in neurons and astrocytes in primary culture. FEBS Lett. 2003;.548: 69–73.
Castagne V, Maire J-C, Moennoz D, Gyger M. Effect of threonine on the behavioural development of the rat. Pharmacol Biochem Be. 1995; 52: 281–289.
Sakagami H, Satoh M, Yokote Y, Takano H, Takahama M, Kochi M et al. Amino acid utilization during cell growth and apoptosis induction. Anticancer Res. 1998; 18:4303–4306.