Hyman, Bradley T

Publication Detail

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No association between a presenilin 1 polymorphism and Alzheimer disease.

S N Romas; R Mayeux; M X Tang; R Lantigua; M Medrano; B Tycko; J Knowles (Profiled Author: Mayeux, Richard)

Gertrude H. Sergievsky Center, Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Archives of neurology 2000;57(5):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-epsilon4, 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-epsilon4 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.

3 Originating Grant

• 1.

  MAYEUX, RICHARD

  Genetic Epidemiology of Alzheimer's Disease in Hispanics

  1 December 1998 - 31 January 2014

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 10,703,458

• 2.

  Mayeux, Richard P

  GENETIC EPIDEMIOLOGY OF ALZHEIMERS DISEASE IN HISPANICS

  1 December 1998 - 31 January 2004

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 5,549,515

• 3.

  Mayeux, Richard

  Epidemiology of Dementia In An Urban Community

  1 February 1989 - 30 June 2009

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 40,531,208

Scientific Context

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