Alzheimer's disease (AD) is a complex disease with the possible involvement of several genes. Genetic studies on sporadic late-onset AD have determined APOE*4 to be the major risk factor. Members of the synuclein gene family are potential candidates for the risk of AD. The persyn gene (gamma-synuclein) has recently been characterized and a common polymorphism (Glu110Val) has been identified. In this study we investigated the association of this polymorphism with sporadic late-onset AD patients. We screened DNA samples of 313 late-onset cases and 352 controls. No significant association was observed between the missense mutation and AD. When the data were stratified by APOE*4 carriers and non-APOE*4 carriers, no difference was seen for the Glu110Val polymorphism. There was also no difference in genotype or allele frequency when stratified by the ACT*A allele. Although our data show no effect of this persyn polymorphism in AD, characterization of additional polymorphisms in this gene may provide more conclusive answers.