The dysfunction of the cholinergic system in Alzheimer's disease (AD) supports the hypothesis that a decline in choline acetyltransferase (ChAT) activity in memory as well as in cognitive functions in AD might be functionally linked. To assess the physiological relevance of an allelic variation in the ChAT gene we investigated the presence of a possible polymorphism in AD patients and in elderly non-demented subjects as controls. By using polymerase chain reaction, single stranded conformation polymorphism or the LightCycler analysis we detected a single nucleotide polymorphism in the first common coding exon of the ChAT gene. We found a G --> A transition which occurred at position +4 of the coding sequence. The association between AD and the AA genotype or A alleles were found to be significant (odds ratio 3.7 and 2.4, respectively). The frequency of the AA genotype was three times higher in AD patients than in age-matched controls. This G --> A change raises the possibility that it may influence ATG usage resulting in attenuation of translation efficacy of ChAT messenger RNA. We suggest that such a polymorphism might be one of the events conferring an increased risk for deterioration of memory and cognition functions in AD.