Altered Circulating Free Oxysterols in Mild Cognitive Impairment: Relationship to Diet, Lipids and Genetics

BackgroundOxysterols, products of cholesterol oxidation, seem dysregulated in Alzheimer’s disease (AD) and mild cognitive impairment (MCI). However, little is known about serum free oxysterol (biologically active form) profiles for MCI.MethodsSerum free oxysterol profiles were measured by ultra-performance liquid chromatography-mass spectrometry in discovery (n = 145) and validation batch (n = 356), both of which were constituted with cognitively normal individuals and MCI patients. We assessed associations of oxysterols with demographics, cognition, diet, lipids and genetics.Results27-Hydroxycholesterol and 7α-hydroxy-3-oxo-4-cholestenoic acid could distinguish MCI from control with good performance in both discovery batch (AUC = 0.80) and validation batch (AUC = 0.71). MCI status could affect correlation patterns among oxysterols, cognition and lipids. Genetic variants in APOE, CYP27A1, CYP46A1 showed inverse associations with cognition and lipids/oxysterol levels while CYP7A1 showed consistent associations.ConclusionsWe identify for the first time an altered free oxysterol profile and report associations with genetic variants in MCI using two-step case-control studies.Trial registration: EMCOA, ChiCTR-OOC-17011882, Registered 5th, July 2017-Retrospectively registered, http://www.medresman.org/uc/project/projectedit.aspx?proj=2610