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.