Introduction- Alzheimer's disease (AD) is classified as neurodegenerative, progressive and irreversible and is clinically characterized by a progressive decline in neurological functions. Objective- To evaluate the association among the genotypic variations of the APOE gene with Alzheimer's Disease. Methods- This is a systematic review and meta-analysis, and, according to the inclusion criteria, 59 articles were selected from the PubMed, Latin American and Caribbean Literature in Health Sciences (LILACS) and Scientific databases Electronic Library Online (SciELO) and of this total, 22 contributed data for systematic review and meta-analysis. Statistical tests were performed with the aid of the STATA® 16.0 software, considering the significance limit equal to 5% (p-value = 0.05). Thus, the DerSimonian-Laird and Mantel Haenszel tests were applied according to heterogeneity, for the evaluation of Odds Ratios (OR). Results- The results showed an association of predisposition to the development of AD, considering the genotypes Ԑ3Ԑ4 and Ԑ4Ԑ4, respectively OR = 2.63 (95% CI = 2.18-318) and OR = 5.37 (95% CI = 3.57- 8.08), on the other hand, the genotypes Ԑ2Ԑ3 and Ԑ3Ԑ3, showed association as a protective factor against AD, respectively OR = 0.49 (95% CI = 0.42-0.57) and OR = 0.53 (95% CI = 0.42-0.68). Conclusion- The present meta-analysis showed a strong association of risk to AD when the genotype Ԑ4Ԑ4 and genotype Ԑ3Ԑ4 were evaluated, on the other hand, there was an association of protection to AD for Ԑ2Ԑ3 and Ԑ3Ԑ3. The other genotypes showed no association.