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-hydroxycholesterol 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 neurodegeneration. We investigated whether plasma
24S-hydroxycholesterol 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.