Plasma 24S-hydroxycholesterol: a peripheral indicator of neuronal degeneration and potential state marker for Alzheimer's disease

The conversion of brain cholesterol into 24S-hydroxycholesterol and its sub sequent release into the periphery is probably an important step for the ma intenance of brain cholesterol homeostasis. Recent findings suggest that pl asma 24S-hydroxycholesterol may be elevated in Alzheimer's disease (AD) and vascular dementia at least at some stage of the disease, suggesting increa sed brain cholesterol turnover during neurodegeneration. We investigated wh ether plasma 24S-hydroxycholesterol concentrations depend on the severity o f AD and on the apolipoprotein E (apoE) genotype. Severity of AD and inheri tance of the apoE4 allele were independently associated with reduced plasma 24S-hydroxycholesterol/cholesterol ratios. The results suggest that the de crease 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 decre ased activity of the 24S-hydroxylase. Longitudinal studies will assess the validity of the ratio plasma 24S-hydroxycholesterol/cholesterol as a state marker for AD. NeuroReport 11:1959-1962 (C) 2000 Lippincott Williams & Wilk ins.