Plasma 24S-hydroxycholesterol (cerebrosterol) is increased in Alzheimer and vascular demented patients

Alzheimer's disease (AD) is characterized by the presence of senile plaques , neurofibrillary tangles, and neuronal cell loss associated with membrane cholesterol release. 24S-hydroxycholesterol (24S-OH-Chol) is an enzymatical ly oxidized product of cholesterol mainly synthesized in the brain. We test ed the hypothesis that plasma levels of this oxysterol could be used as a p utative biochemical marker for an altered cholesterol homeostasis in the br ain of AD patients. Thirty patients with clinical criteria for AD, 30 healt hy volunteers, 18 depressed patients, and 12 patients with vascular dementi a (non-Alzheimer demented) were studied, Plasma concentrations of 24S-OH-Ch ol were assayed by isotope dilution-mass spectrometry, cholesterol was meas ured enzymatically, and apolipoprotein E (apoE) was genotyped by polymerase chain reaction and restricted fragment length polymorphism. The concentrat ion of 24S-OH-Chol in AD and non-Alzheimer demented patients was modestly b ut significantly higher than in healthy controls and in depressed patients, There was no significant difference in the concentrations of 24S-OH-Chol b etween depressed patients and healthy controls nor between AD and non-Alzhe imer demented patients, The apoE E4 allele influences plasma 24S-OH-Chol. H owever, this influence could be completely accounted for by the elevated pl asma cholesterol in apoE4 hetero- or homozygotes, Plasma 24S-OH-Chol levels correlated negatively with the severity of dementia, AD and vascular demen ted patients appear to have higher circulating levels of 24S-OH-Chol than d epressed patients and healthy controls, We speculate that 24S-OH-Chol plasm a levels may potentially be used as an early biochemical marker for an alte red cholesterol homeostasis in the central nervous system.