In our study, we analyzed the coding and promoter regions of the PIN I gene in a group of I I I Alzheimer's disease (AD) patients looking for a possible genotype-phenotype correlation. The presence of SNPs - which could affect and modify the clinical phenotype of AD patients was also investigated. We identified two single nucleotide polymorphisms (SNPs) at positions -842 (G -> C) and -667 (C -> T) in the promoter region of the PIN1 gene. Our results evidenced a significantly higher percentage of -842C allele carriers in AD subjects with respect to healthy controls. We found that this allele significantly raised the risk of developing AD (OR 3.044, CI 1.42-6.52). The -842 and -667 SNPs were in linkage disequilibriurn and combined to form haplotypes. The CC haplotype conferred a higher risk of developing AD (OR 2.95, confidence interval 1.31-6.82). Finally, protein expression analyses revealed that subjects carrying the -842 CC genotype or the CC haplotype showed reduced levels of the PIN1 protein in peripheral mononuclear cells. (c) 2005 Elsevier Inc. All rights reserved.