Prion protein gene polymorphism M129V represents a known risk factor for Creutzfeldt-Jakob disease. Recently, the meta-analysis revealed that homozygosity at codon 129 is connected with increased risk of Alzheimer's disease (AD). To determine whether M129V polymorphism is a risk factor for AD we analyzed a group of early-onset, and late-onset Polish AD patients. We observed that in LOAD patients there is a statistically significant increase of MM (p=0.0028) and decrease of MV (p=0.0006) genotype frequency, as compared to controls. When both groups were stratified according to APOE4 status, increase of MM and decrease of MV genotype frequency were significant in the LOAD subgroup with no APOE4 (p=0.017, and p=0.018, respectively). In the subgroup with APOE4 allele, only MV genotype frequency was significantly lower, as compared to controls (p=0.035). However, no interaction was found between APOE4 status and M129V polymorphism. We conclude that MM genotype increases LOAD risk in Polish population independently from the APOE4 status.