Quantitative detection of free 24S-hydroxycholesterol, and 27-hydroxycholesterol from human serum

Background: Cholesterol metabolism is important for the maintenance of myelin and neuronal membranes in the central nervous system. Blood concentrations of the brain specific cholesterol metabolite 24S-hydroxysterol to the peripheral metabolite 27-hydroxycholesterol may be useful surrogate markers for neurodegenerative diseases including Alzheimer's disease, Huntington's disease, HIV-Associated Neurocognitive Disorders, and Multiple Sclerosis. However, current methods to isolate hydroxycholesterols are labor intensive, prone to produce variable extraction efficiencies and do not discriminate between free and esterfied forms of hydroxycholesterols. Since free hydroxycholesterols are the biologically active form of these sterols, separating free from esterfied forms may provide a sensitive measure to identify disease-associated differences in brain sterol metabolism. Results: We found that average human serum concentrations were 12.3 +/- 4.79 ng/ml for free 24(s)-hydroxycholesterol and 17.7 +/- 8.5 ng/ml for 27-hydroxycholesterol. Conclusion: Serum measurements of these biologically active oxysterols may be useful surrogate measures for brain health in a variety of neurodegenerative conditions.