Decoying the enemy: soluble receptor for advanced glycation end products and cognitive impairment in neurodegenerative diseases—a systematic review and meta-analysis

Abstract Background Accumulation of advanced glycation end products (AGEs) has contribution in development of Alzheimer’s disease (AD), vascular dementia (VAD), and mild cognitive impairment (MCI). AGEs activate several signaling pathways that have roles in development of those diseases via receptor for advanced glycation end product (RAGE), this receptor has its soluble form called sRAGE which has ability to bind AGEs but could not induce molecular signaling. Based on this property, sRAGE could work as RAGE decoy and prevent pathological effect of AGEs accumulation. This meta-analysis is aimed to evaluate correlation between sRAGE plasma level and risk of AD, VAD, and MCI. Methods Standardized mean difference with 95% coincidence interval was used as effect size. Inverse variance was used as analysis method with random effect model. Egger test and funnel plot were used to assess publication bias. Results We found 424 articles through database searching. Among those articles, 15 articles that fulfilled our eligibility criteria. After selection based on inclusion and exclusion criteria, only 5 articles were included in this meta-analysis. Our analysis found that AD and VAD patients have lower levels of plasma sRAGE when compared to healthy control. Significant correlation between low sRAGE plasma level and MCI was not found. However, publication bias is found in MCI group. Publication bias of VAD group could not be assessed due to limited number of studies. Conclusions Here, we show inverse relationship between sRAGE and the incidence of AD alongside VAD suggests that lower sRAGE plasma levels may be associated with a higher incidence of AD and VAD. However, some limitations in sample size and minimal studies may introduce bias into our results.