A comprehensive analysis of MAPT-related genetic risk in Alzheimer’s disease

Despite some research into the correlation between microtubule associated protein tau (<i>MAPT</i>) rs2471738 and the risk of AD, the findings remain inconclusive. The aim of this study was to explore the association between <i>MAPT</i> rs2471738 and the susceptibility to AD, as well as potential molecular mechanisms involved. We conducted a comprehensive literature search on Embase, Medline, and Web of Science to investigate the relationship between <i>MAPT</i> rs2471738 and the risk of AD. We employed meta-analysis and Expression Quantitative Trait Loci analysis to elucidate the association between <i>MAPT</i> rs2471738 and AD risk, as well as to uncover potential molecular mechanisms. Aggregated results suggest that the rs2471738T allele increases the risk of developing AD under the allelic model (odds ratio [OR] = 1.15, 95 % confidence interval [CI] = 1.04-1.26, I² = 64.9 %). Additionally, our findings indicate that the rs2471738CT+TT genotype escalates the risk of AD under the dominant model (OR = 1.23, 95 % CI = 1.07-1.41, I² = 79.2 %). Moreover, rs2471738 regulates the expression of <i>MAPT</i> in the human hippocampus (<i>P</i> = 0.04). Our result suggested that rs2471738 may potentially increase the risk of AD by modulating the expression of <i>MAPT</i> in human brain tissue.