APOLIPOPROTEIN-E EPSILON-2 ALLELE PROMOTES LONGEVITY AND PROTECTS PATIENTS WITH DOWNS-SYNDROME FROM DEMENTIA

ALTHOUGH individuals with Down's syndrome nearly always develop the cl inical and pathological features of Alzheimer's disease, some clearly do not become demented despite living into their sixth and seventh dec ades. Genetic variation at the apolipoprotein E locus has recently bee n shown to be an important determinant of Alzheimer's disease, with th e epsilon 4 allele having been shown to be associated with the disease and, at least in some cases, the epsilon 2 allele being negatively as sociated with the disease. Here we show, in a series of clinically ass essed individuals with Down's syndrome, that the epsilon 2 allele of A poE is associated with both longevity and the absence of clinical evid ence of dementia. These data show that the clinical phenotype of Down' s syndrome can be modulated by genes on chromosomes other than chromos ome 21. The importance of this observation to the pathogenesis of Alzh eimer's disease, both in Down's syndrome and in general, is discussed.