Plasma oxyphytosterols most likely originate from hepatic oxidation and subsequent spill-over in the circulation.

We evaluated oxyphytosterol (OPS) concentrations in plasma and various tissues of two genetically modified mouse models with either increased cholesterol (apoE KO mice) or increased cholesterol and plant sterol (PS) concentrations (apoExABCG8 dKO mice). Sixteen female apoE KO and 16 dKO mice followed the same standard, low OPS-chow diet. Animals were euthanized at 36 weeks to measure PS and OPS concentrations in plasma, brain, liver and aortic tissue. Cholesterol and oxysterol (OS) concentrations were analyzed as reference for sterol oxidation in general. Plasma campesterol (24.1 ± 4.3 vs. 11.8 ± 3.0 mg/dL) and sitosterol (67.4 ± 12.7 vs. 4.9 ± 1.1 mg/dL) concentrations were severely elevated in the dKO compared to the apoE KO mice (p < 0.001). Also, in aortic and brain tissue, PS levels were significantly elevated in dKO. However, plasma, aortic and brain OPS concentrations were comparable or even lower in the dKO mice. In contrast, in liver tissue, both PS and OPS concentrations were severely elevated in the dKO compared to apoE KO mice (sum OPS: 7.4 ± 1.6 vs. 4.1 ± 0.8 ng/mg, p < 0.001). OS concentrations followed cholesterol concentrations in plasma and all tissues suggesting ubiquitous oxidation. Despite severely elevated PS concentrations, OPS concentrations were only elevated in liver tissue, suggesting that OPS are primarily formed in the liver and plasma concentrations originate from hepatic spill-over into the circulation.

Altered levels of plasma 24S- and 27-hydroxycholesterol in demented patients.

Alterations in brain cholesterol metabolism and reduced 24S-hydroxycholesterol plasma levels have been described in Alzheimer's disease (AD) and vascular dementia (VD). We hypothesize that changes in peripheral cholesterol metabolism, such as alterations in the plasma levels of 27-hydroxycholesterol, might also be involved. Plasma levels of 24S-hydroxycholesterol and 27-hydroxycholesterol in patients suffering from dementing disorders such as AD, VD, and mild cognitive impairment (MCI) were compared to those in age- and cholesterol matched non-demented and depressed subjects. Cholesterol corrected concentrations of plasma 24S-hydroxycholesterol and 27-hydroxycholesterol were significantly reduced in patients with dementing disorders compared to non-demented subjects and depressed patients. A strong positive correlation between plasma 24S-hydroxycholesterol and 27-hydroxycholesterol levels was observed. The ratios of plasma 24S-hydroxycholesterol to 27-hydroxycholesterol were higher in patients with dementing disorders compared to non-demented subjects. Our results support the observation, that cholesterol metabolism is altered in dementing disorders, indicated by different plasma concentrations of brain specific and peripherally produced oxysterols.