title: Plasma 24S-hydroxycholesterol correlation with markers of Huntington disease progression.
abstract: 24S-hydroxycholesterol (24OHC) is involved in the conversion of excess cholesterol in the brain, and its level in plasma is related to the number of metabolically active neuronal cells. Previous research suggests that plasma 24OHC is substantially reduced in the presence of neurodegenerative disease. Huntington disease (HD) is an inherited autosomal dominant neurodegenerative disorder caused by a cytosine-adenine-guanine (CAG) triplet repeat expansion in the coding region of the huntingtin (HTT) gene. The current study focused on the relative importance of 24OHC as a marker of HD progression. Using mass spectrometry methods, we examined plasma 24OHC levels in three groups of gene-expanded individuals (Low, Medium, High) characterized by their progression at entry into the parent PREDICT-HD study, along with a group of non-gene-expanded controls (total N=150). In addition, the correlation of 24OHC with a number of motor, cognitive, and imagining markers was examined, and effect sizes for group differences among the markers were computed for comparison with 24OHC. Results show a progression gradient as 24OHC levels decreased as the progression group increased (Low to High). The effect size of group differences for 24OHC was larger than all the other variables, except striatal volume. 24OHC was significantly correlated with many of the other key variables. The results are interpreted in terms of cholesterol synthesis and neuronal degeneration. This study provides evidence that 24OHC is a relatively important marker of HD progression.
authors.affiliation: Laboratory of Clinical Pathology and Medical Genetics, Fondazione IRCCS Institute of Neurology Carlo Besta, Milan, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Leoni
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Long
authors.forename: James A
authors.initials: JA
authors.lastname: Mills
authors.forename: Stefano
authors.initials: S
authors.lastname: Di Donato
authors.forename: Jane S
authors.initials: JS
authors.lastname: Paulsen
mesh_terms: D000328:Adult; D003072:Cognition Disorders / Q000209:etiology; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006816:Huntington Disease / Q000097:blood* / Q000235:genetics / Q000503:physiopathology*; D006888:Hydroxycholesterols / Q000097:blood*; D007391:International Cooperation; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D013223:Statistics as Topic; D014706:Verbal Learning
chemical_list: D006888:Hydroxycholesterols; C044563:24-hydroxycholesterol
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