Circulating oxysterols in Alzheimer's disease: a systematic review and meta-analysis

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.