No association between a presenilin 1 polymorphism and Alzheimer disease

Background: Homozygosity of allele 1 of a presenilin 1 intron 8 polymorphis m (PSI-I) has been associated with doubling of the risk of sporadic lace-on set Alzheimer disease (LOAD), in some, but not all studies. Objective: To genotype the PS1 intron 8 polymorphism in predominantly Hispa nic families with LOAD to test for association and for linkage between this polymorphism and LOAD. Design: A family-based, case-control, genetic-linkage study. Setting: Predominantly Hispanic families were selectcd from probands who we re part of a random sample of 2128 Medicare beneficiaries aged 65 years or older who were residing in the community of Washington Heights, which is lo cated in the northern part of Manhattan, NY. Participants: Fifty-one families with 103 affected family members, 67 unaff ected family members, and 7 family members with other diagnoses were genoty ped for the PSI polymorphism. All patients met National Institute of Neurol ogical and Communicative Disorders and Stroke-Alzheimer's Disease and Relat ed Disorders Association criteria for either probable or possible Alzheimer disease. Age was truncated at 55 years or older. Main Outcome Measures: Association analyses, conditional logistic regressio n, and traditional linkage methods were applied to the families for the PSI polymorphism and for the presence of the gene for apolipoprotein E (APOE). Results of the association and conditional logistic regression analyses of PS I intron 8 polymorphism were subsequently adjusted for the effect of APO E-epsilon 4, sex, age, and education of Each sibling. Results: No associati on between the PS1 intron 8 polymorphism and LOAD was observed (relative ri sk, 0.99; 95% confidence interval, 0.3-3.4). An association between presenc e of the APOE-epsilon 4 allele and LOAD (relative ris1- 4.05; 95% confidenc e interval, 1.3-12.5) was observed. Conclusion: We could not confirm the relationship between the PSI intron 8 polymorphism and LOAD in this collection of families.