In the second meta-analysis, studies by Zhao et al.21, Lesiak et al.26, Dębińska et al.30, and González-Tarancón et al.35, reported statistically significant results regarding the odds of AD development, primarily by evaluating FLG and SPINK5. Both meta-analyses strongly suggested that variants of SPINK5 and FLG may play a crucial role in AD development. This evidence concerns the gene FLG and Alzheimer disease.