A panel of altered blood oxysterols in patients with mild cognitive impairment: A novel combined diagnostic marker

Perturbed cholesterol metabolism may play an important role in the development of dementia and its preclinical stage, mild cognitive impairment (MCI). Oxysterols, the metabolites generated during cholesterol oxidation, also appear to be risk factors for MCI. Therefore, we aimed to investigate if the metabolic profile of blood oxysterols could be used to characterize MCI risk. This cross-sectional study incorporated 501 participants-253 patients with MCI and 248 cognitively normal controls. Serum levels of 22 free oxysterols were measured, and a set of 27 oxysterol-related gene polymorphisms was genotyped. Five [27-hydroxycholesterol (27-OHC), 27-OHC periphery-derived metabolite 3β-hydroxy-5-cholestenoic acid (27-CA) and brain-derived metabolite 7α-hydroxy-3-oxo-4-cholestenoic acid (7-HOCA), 4β-hydroxycholesterol (4β-OHC); 4α-hydroxycholesterol (4α-OHC)] of the twenty-two oxysterols detected in serum significantly differed between the patients with MCI and controls, greatly distinguishing patients with MCI from control individuals (AUC=0.834, 95 % CI: 0.804-0.866). Association analyses demonstrated significant correlations between these candidate oxysterol biomarkers with younger age, higher blood lipids, worse cognitive performance, and higher monounsaturated fatty acid intake. This panel of serum free oxysterols as candidate serum oxysterol biomarkers for MCI highlighted the essential role of 27-OHC in the pathogenesis of early dementia prevention. (The study registered in the Chinese Clinical Trial Registry as ChiCTR-OOC-17011882).