TY - JOUR
T1 - Whole body cholesterol metabolism is impared in Huntington's disease.
AU - Bentivoglio, Anna Rita
AU - Leoni, V.
AU - Mariotti, C.
AU - Nanetti, L.
AU - Salvatore, E.
AU - Squitieri, F.
AU - Bandettini Del Poggio, M.
AU - Piacentini, S.
AU - Monza, D.
AU - Valenza, M.
AU - Cattaneo, E.
AU - Di Donato, S.
PY - 2011
Y1 - 2011
N2 - 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
AB - 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
KW - Atrophy
KW - HUNTINGTON'S DISEASE
KW - Metabolism
KW - Neurodegeneration
KW - Atrophy
KW - HUNTINGTON'S DISEASE
KW - Metabolism
KW - Neurodegeneration
UR - http://hdl.handle.net/10807/3159
U2 - 10.1016/j.neulet.2011.03.025
DO - 10.1016/j.neulet.2011.03.025
M3 - Article
SN - 0304-3940
VL - 2011
SP - 245
EP - 249
JO - Neuroscience Letters
JF - Neuroscience Letters
ER -