Plasma 24S-hydroxycholesterol correlation with markers of Huntington disease progression

Valerio Leoni, Jeffrey D. Long, James A. Mills, Stefano Di Donato, Jane S. Paulsen

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)37-43
Number of pages7
JournalNeurobiology of Disease
Volume55
DOIs
Publication statusPublished - Jul 2013

Fingerprint

Huntington Disease
Disease Progression
Neurodegenerative Diseases
Cholesterol
Trinucleotide Repeats
Corpus Striatum
Cytosine
Guanine
Adenine
Genes
Mass Spectrometry
24-hydroxycholesterol
Brain
Research

Keywords

  • Biomarkers
  • Cholesterol
  • Huntington disease
  • Neurodegenerative disease

ASJC Scopus subject areas

  • Neurology

Cite this

Plasma 24S-hydroxycholesterol correlation with markers of Huntington disease progression. / Leoni, Valerio; Long, Jeffrey D.; Mills, James A.; Di Donato, Stefano; Paulsen, Jane S.

In: Neurobiology of Disease, Vol. 55, 07.2013, p. 37-43.

Research output: Contribution to journalArticle

Leoni, Valerio ; Long, Jeffrey D. ; Mills, James A. ; Di Donato, Stefano ; Paulsen, Jane S. / Plasma 24S-hydroxycholesterol correlation with markers of Huntington disease progression. In: Neurobiology of Disease. 2013 ; Vol. 55. pp. 37-43.
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