Huntington’s disease (chorea, HD) is a hereditary disease, which causes death of neurons in certain parts of the brain. Since 1993 its genetic basis has been known and it is associated with IT15 gene mutation on chromosome 4 encoding the huntingtin protein. The disease symptoms are involuntary movements and dementia. While HD progresses, the patient loses the ability to control the body movements, emotions and thinking. The patients with HD have a poor prognosis: the disease inevitably leads to death within 10 to 20 years since the occurrence of the first symptoms.

The pathogenetic factors responsible for the development of the disease include transcriptional deregulation and impaired energy metabolism. The metabolic defect is potentially associated, among other things, with decreased levels of branched-chain amino acids (valine, isoleucine and leucine), which are indirectly involved in the energy-giving Krebs cycle and the respiratory chain.

The purpose of this work was to determine the plasma amino acid profiles in a control group and in HD patients and to identify the amino acids which in time could prove to be HD biomarkers. Defining biomarkers of this neurodegenerative disease could help to early diagnose HD, to monitor the progression of changes and to assess the administered neuroprotective therapy.

For this purpose, blood samples were collected from 30 patients with HD and 29 healthy controls (approval of the Bioethics Committee at the Poznań University of Medical Sciences No. 770/09).

Plasma samples deproteinized by ultrafiltration and a model mixture of amino acids were submitted to the derivatization reaction with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC). The obtained stable derivatives were tested by the gradient HPLC method using a fluorescence detector (E_X = 250 nm, E_M = 396 nm). As the quantitative assessment of amino acids in biological material requires a highly selective method, an ion-pairing mechanism was used, due to using a triethylamine buffer with additional N,N-dimethyloctylamine in the mobile phase. The separation conditions were optimized by selecting the appropriate pH value, column temperature, counterion concentration and acetonitrile gradient. The presented chromatographic conditions allowed separation and quantitative determination of 23 amino acids.

The statistical analysis of the obtained results was performed using the SYSTAT software for Windows, version 13.00.05 (SYSTAT Inc., USA). The use of the non-parametric Mann-Whitney test helped to demonstrate that 5 amino acids (asparagine, histidine, leucine, serine, threonine) have significantly lower plasma levels in patients with HD as compared to healthy controls (p<0.05, α=0.05).

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