Background: Alzheimer's disease (AD) is the most common cause of dementia in the elderly, and its etiology is still not fully understood. The aim of this study was to analyze the role of the genetic variants of two synaptic vesicle proteins (VAMP2, synapsin III) and two presynaptic plasma membrane proteins (syntaxin 1A, SNAP-25) in AD patients. We analyzed the functional polymorphisms of VAMP2, synapsin III, syntaxin 1A, and SNAP-25 genes. Method: Sixty-eight adult patients with Alzheimer disease and Seventy-eight healthy adults were included in the study. DNA was extracted from whole blood by the salting out procedure. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. We determined alleles and the genotypes of polymorphism of VAMP2, synapsin III, SNAP-25 and syntaxin 1A genes. Results: We observed significant differences in the genotypic distribution of the Synapsin III rs 133945 polymorphism for AD compared with that in controls. Also, we found significant differences in the allelic distribution of the Synapsin III rs 133946 polymorphism for AD compared with controls. We have found that individuals who have G alleles are 1.5 times more at risk of developing AD than those with C alleles. Exon 3 polymorphism of syntaxin 1A gene is associated with AD. Individuals who have T alleles are 1.7 times more at risk of developing AD than those with C alleles. In addition, result of logistic regression analysisSNAP-25 and Synapsin III is significant in relevance with AD. Conclusion: The present results indicate the possible contribution of VAMP2, synapsin III, syntaxin 1A and SNAP-25 gene polymorphisms to AD.