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Despite decades of research, the cause and series of events underlying the advancement of Alzheimer’s disease (AD) have not yet been established. Lipid, especially cholesterol, levels have been proposed to be implicated in AD. Several studies have been undertaken and many are ongoing in different directions looking at the importance of circulating cholesterols and oxidised cholesterols in AD with inconsistent methods and results. This meta-analysis aims to systematically analyse available data describing the involvement of oxidised cholesterols in mild cognitive impairment (MCI) and AD. We conducted a systematic literature search of six databases MEDLINE (PubMed), BIOSIS (Web of Science), EMBASE (Elsevier), PsycNET, Scopus and Cochrane library for studies measuring oxysterols (24-hydroxycholesterol (24OHC); 26-hydroxycholesterol (26OHC) and 7-oxycholesterols) in serum or plasma from MCI/AD patients compared to age- and gender-matched cognitively normal controls. Data were analysed using the inverse variance and standard mean difference with random-effect analysis model at 95% CI for association between oxysterols and MCI/AD in Review Manager (RevMan) software version 5.4.1. Between January 2000 and April 2022, 175 studies were identified by two independent researchers out of which 14 met the inclusion criteria and were analysed with a total of 957 controls, 469 MCI cases and 509 AD cases. The standard mean differences between MCI/AD participants and controls did not show any difference in the oxysterol levels except for 26OHC level which was higher in AD but not statistically significant.
Lab-NAFS ‘Nutrition-Functional Food & Vascular Health’, Faculty of Medicine, University of Monastir, Monastir, Tunisia
Faculty of Sciences of Tunis, University Tunis-El Manar, Tunis, Tunisia
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Faculty of Medicine, University of Sousse, Sousse, Tunisia
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Department of Biology, Faculty of Sciences, University Tunis-El Manar, Loboratory of Neurophysiology, Cellular Physiopathology and Valorisation of BioMolecules, LR18ES03, Tunis, Tunisia
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Laboratory of Biochemistry, Neurosciences, Natural Resources and Environment, Faculty of Sciences & Techniques, University Hassan I, Settat, Morocco
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Laboratory of Biochemistry, Neurosciences, Natural Resources and Environment, Faculty of Sciences & Techniques, University Hassan I, Settat, Morocco
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University of Carthage, High Institute of Food Industries, El Khadra City, Tunis, Tunisia
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Graphical abstract
Abstract
7-Ketocholesterol (or 7-oxocholesterol) is an oxysterol essentially formed by cholesterol autoxidation. It is often found at enhanced levels in the body fluids and/or target tissues of patients with age-related diseases (cardiovascular, neuronal, and ocular diseases) as well as in subjects concerned with civilization diseases (type 2 diabetes, bowel diseases, and metabolic syndrome). The involvement of increased 7-ketocholesterol levels in the pathophysiology of these diseases is widely suspected. Indeed, 7-ketocholesterol at elevated concentrations is a powerful inducer of oxidative stress, inflammation, and cellular degeneration which are common features of all these diseases. It is important to better know the origin of 7-ketocholesterol (diet, incidence of environmental factors, and endogenous formation (autoxidation and enzymatic synthesis)) and its inactivation mechanisms which include esterification, sulfation, oxidation, and reduction. This knowledge will make it possible to act at different levels to regulate 7-ketocholesterol level and counteract its toxicity in order to limit the incidence of diseases associated with this oxysterol. These different points as well as food and biomedical applications are addressed in this review.
