Plasma 24S-hydroxycholesterol

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Abstract
The conversion of brain cholesterol into 24S-hydroxycholesterol and its subsequent release into the periphery is probably an important step for the maintenance of brain cholesterol homeostasis. Recent findings suggest that plasma 24S-hydro-xycholesterol may be elevated in Alzheimer's disease (AD) and vascular dementia at least at some stage of the disease, suggesting increased brain cholesterol turnover during neuro-degeneration. We investigated whether plasma 24S-hydroxy-cholesterol concentrations depend on the severity of AD and on the apolipoprotein E (apoE) genotype. Severity of AD and inheritance of the apoE4 allele were independently associated with reduced plasma 24S-hydroxycholesterol/cholesterol ratios. The results suggest that the decrease of plasma 24S-hydroxycholesterol/cholesterol in severely affected AD patients is a peripheral marker for loss of cholesterol 24S-hydroxylase in the CNS. Inheritance of the apoE4 allele may be associated with increased apoE-mediated transport of brain cholesterol to the periphery or with decreased activity of the 24S-hydroxylase. Longitudinal studies will assess the validity of the ratio plasma 24S-hydroxycholesterol/cholesterol as a state marker for AD.