IL-33/ST2 signaling pathway and Alzheimer's disease: A systematic review and meta-analysis

The IL-33/ST2 signaling pathway has potential relevance for clinical identification and treatment of Alzheimer's disease (AD). Here, eight databases (including CNKI, Wanfang, SinoMed, VIP, PubMed, Cochrane library, Embase and Web of Science) were employed to search for studies on IL-33/ST2 signaling pathway and its association with AD. Totally, 15 articles were included, of which 5 studies investigated the connection between IL-33 gene polymorphisms and AD, 4 studies explored the serum IL-33 and sST2 levels in patients with AD and Mild cognitive impairment (MCI), and the exact mechanisms underlying IL-33/ST2 signaling pathway in AD were explored in 6 studies. Then, the RevMan 5.4 software was used for meta-analysis, and the related studies were systematically reviewed. The results of the meta-analysis showed that serum IL-33 levels were higher in patients with AD and MCI than in healthy controls (HC), with serum IL-33 levels in AD patients significantly higher than in MCI patients (SMD = 0.26, 95 % CI: 0.02, 0.51; P = 0.04). Compared with HC, the sST2 level was significantly higher in AD patients (SMD = 1.23, 95 % CI: 0.93, 1.53; P < 0.00001) and tended to elevate in patients with MCI. The systematic review indicated that there is a significant relationship between IL-33 gene polymorphisms and susceptibility to AD; The IL-33/ST2 signaling pathway may be one of the future treatment targets for AD. Our study provides evidence to prove that serum IL-33 and sST2 have potential clinical application value as biomarkers for identifying AD.