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Stavra Nicole Romas, MD; Richard Mayeux, MD, MSc; Ming-Xin Tang, PhD; Rafael Lantigua, MD; Martin Medrano, MD; Benjamin Tycko, MD, PhD; James Knowles, MD, PhD

Arch Neurol. 2000;57:699-702.

Background  Homozygosity of allele 1 of a presenilin 1 intron 8 polymorphism (PS1-1) has been associated with doubling of the risk of sporadic late-onset Alzheimer disease (LOAD), in some, but not all studies.

Objective  To genotype the PS1 intron 8 polymorphism in predominantly Hispanic 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 selected from probands who were 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 located in the northern part of Manhattan, NY.

Participants  Fifty-one families with 103 affected family members, 67 unaffected family members, and 7 family members with other diagnoses were genotyped for the PS1 polymorphism. All patients met National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related 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 regression, and traditional linkage methods were applied to the families for the PS1 polymorphism and for the presence of the gene for apolipoprotein E (APOE). Results of the association and conditional logistic regression analyses of PS1 intron 8 polymorphism were subsequently adjusted for the effect of APOE-4, sex, age, and education of each sibling.

Results  No association between the PS1 intron 8 polymorphism and LOAD was observed (relative risk, 0.99; 95% confidence interval, 0.3-3.4). An association between presence of the APOE-4 allele and LOAD (relative risk, 4.05; 95% confidence interval, 1.3-12.5) was observed.

Conclusion  We could not confirm the relationship between the PS1 intron 8 polymorphism and LOAD in this collection of families.

From the Taub Alzheimer's Disease Research Center, Gertrude H. Sergievsky Center (Drs Romas, Mayeux, Tang, and Knowles), and the Departments of Neurology (Drs Romas and Mayeux), Psychiatry (Drs Mayeux and Knowles), Medicine (Dr Lantigua), and Pathology (Division of Neuropathology) (Dr Tycko), Columbia University College of Physicians and Surgeons, and the Columbia Genome Center (Dr Knowles) and the Divisions of Epidemiology (Dr Mayeux) and Biostatistics (Dr Tang), School of Public Health, Columbia University, New York, NY; and the Department of Medicine, Universidad Tecnologica de Santiago, Santiago de los Caballeros, Dominican Republic (Dr Medrano).

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