title: Whole body cholesterol metabolism is impaired in Huntington's disease.
abstract: We previously reported impaired cholesterol biosynthesis in rodent Huntington Disease (HD) models and HD patients' fibroblasts and post mortem brains. We also found that plasma levels of 24S-hydroxycholesterol (24OHC), the brain specific elimination product of cholesterol considered a marker of brain cholesterol turnover, were significantly reduced in HD patients at any disease stage. In the present study we analysed by mass spectrometry the fasting plasma levels of cholesterol, its biosynthetic precursors lanosterol and lathosterol, of the whole-body elimination products 27-hydroxycholesterol and of brain 24OHC in a cohort of premanifest and HD patients at different disease stages. We found that the cholesterol precursors lanosterol and lathosterol (both index of whole body cholesterol synthesis), the levels of the bile acid precursor 27-hydroxycholesterol, and of the brain specific 24OHC, were all significantly reduced in manifest HD patients, suggesting that whole-body and brain cholesterol homeostasis are both impaired in HD.
authors.affiliation: Laboratory of Clinical Pathology and Medical Genetics, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Via Celoria 11, 20133 Milano, MI, Italy. valerioleoni@hotmail.com
authors.forename: V
authors.initials: V
authors.lastname: Leoni
authors.forename: C
authors.initials: C
authors.lastname: Mariotti
authors.forename: L
authors.initials: L
authors.lastname: Nanetti
authors.forename: E
authors.initials: E
authors.lastname: Salvatore
authors.forename: F
authors.initials: F
authors.lastname: Squitieri
authors.forename: A R
authors.initials: AR
authors.lastname: Bentivoglio
authors.forename: M
authors.initials: M
authors.lastname: Bandettini di Poggio
authors.forename: M
authors.initials: M
authors.lastname: Bandettini Del Poggio
authors.forename: S
authors.initials: S
authors.lastname: Piacentini
authors.forename: D
authors.initials: D
authors.lastname: Monza
authors.forename: M
authors.initials: M
authors.lastname: Valenza
authors.forename: E
authors.initials: E
authors.lastname: Cattaneo
authors.forename: S
authors.initials: S
authors.lastname: Di Donato
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D002784:Cholesterol