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Mortality is associated with apolipoprotein E epsilon4 in nondemented adults with Down syndrome.

Zigman WB, Jenkins EC, Tycko B, Schupf N, Silverman W

New York State Institute For Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314-6399, USA. wbzigman@aol.com

Apolipoprotein E genotype has been related to survival in the general population, but its strong association with Alzheimer's disease (AD) makes interpretation of findings difficult. Previous studies of adults with Down syndrome (DS) have consistently found that the presence of the apolipoprotein E epsilon2 allele increases longevity and reduces the risk of dementia, while the apolipoprotein E epsilon4 allele increases risk for dementia. In contrast, reduced frequencies of the apolipoprotein E epsilon4 allele among elderly groups have been reported, suggesting that the epsilon4 allele may be associated with early mortality in this population. To disentangle effects of dementia from those of aging, per se, we compared mortality risk as a function of apolipoprotein E genotype in 146 nondemented adults with DS in a prospective study. Individuals with at least one epsilon4 allele were approximately five times more likely to die within a 5- to 7-year follow-up period than those without an epsilon4 allele, adjusting for age, sex, body mass index, level of mental retardation, and cholesterol level. These results suggest that the apolipoprotein E epsilon4 allele has an independent and strong relation to early mortality.

Published 10 October 2005 in Neurosci Lett, 390(2): 93-7.
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