Association of F 2 -isoprostane levels with Alzheimer’s disease in observational studies: A systematic review and meta-analysis

The association between F 2 -isoprostanes and Alzheimer’s disease (AD) has been controversially discussed in the literature since the 1990s. However, no systematic review has been performed so far. A systematic review of observational studies on the associations of F 2 -isoprostanes and the specific biomarker 8-iso-prostaglandin F 2α with AD were conducted. Random-effects model meta-analyses were performed. 29 studies were included in the systematic review, including four longitudinal studies. In an overall meta-analysis of the 25 cross-sectional studies, F 2 -isoprostane levels were statistically significantly associated with AD (Hedge’s g [95% confidence interval]: 1.00 [0.69–1.32]). When studies were grouped by biomarker and sample specimen, F 2 -isoprostane and 8-iso-prostaglandin F 2α levels were statistically significantly elevated in tissue samples of the frontal lobe of AD patients. Moreover, F 2 -isoprostane levels in cerebrospinal fluid and 8-iso-prostaglandin F 2α levels in blood samples of AD patients were significantly increased. Meta-analyses of the few longitudinal studies did not reach statistical significance. Increased concentrations of F 2 -isoprostanes were found in AD patients. However, due to the lack of adjustment in most cross-sectional case-control studies, results must be interpreted carefully. In addition, the causality of the association is uncertain because evidence from well-conducted longitudinal studies was conflicting, and further longitudinal studies are required to reinforce the results.