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Alteration of brain cholesterol synthesis and metabolism has been demonstrated in several Huntington's disease (<jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>) mouse and cell models; however, less is known about these alterations in human tissue. This study aimed to identify alterations to cholesterol synthetic and metabolic pathways in human <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> brain tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A broad range of cholesterol synthetic precursors, metabolites and oxidation products were measured by gas chromatography\u2010tandem mass spectrometry in five regions of human <jats:italic>post mortem<\/jats:italic>\u2005<jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> brain and compared with age\u2010 and sex\u2010matched control tissues. The level of enzymes that regulate cholesterol homeostasis, cholesterol 24\u2010hydroxylase and delta(24)\u2010sterol reductase were investigated by <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>estern blotting and <jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content> in putamen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The most significant changes were localized to the putamen, where a 60% decrease in 24(<jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>)\u2010hydroxycholesterol, 30% increase in cholesterol and 100\u2013200% increase in synthetic precursors (lathosterol, zymosterol and desmosterol) was detected. The enzymes cholesterol 24\u2010hydroxylase and delta(24)\u2010sterol reductase were also significantly decreased in <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> putamen as compared with control tissues. Free radical\u2010generated cholesterol oxidation products 7\u2010keto cholesterol and 7\u03b2\u2010hydroxycholesterol were also increased by 50\u201370% in <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> putamen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Human <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> brain has significantly decreased cholesterol metabolism and disrupted cholesterol homeostasis. Our data also indicate that lipid oxidative stress accompanies <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> pathology.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12286","type":"journal-article","created":{"date-parts":[[2015,9,16]],"date-time":"2015-09-16T07:02:43Z","timestamp":1442386963000},"page":"535-546","source":"Crossref","is-referenced-by-count":91,"title":["Evidence for altered cholesterol metabolism in <scp>H<\/scp>untington's disease <i>post mortem<\/i> brain tissue"],"prefix":"10.1111","volume":"42","author":[{"given":"Fabian","family":"Kreilaus","sequence":"first","affiliation":[{"name":"Illawarra Health and Medical Research Institute University of Wollongong  Wollongong Australia"},{"name":"School of Biological Sciences University of Wollongong  Wollongong Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adena S.","family":"Spiro","sequence":"additional","affiliation":[{"name":"Illawarra Health and Medical Research 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