A PROTECTIVE EFFECT OF APOLIPOPROTEIN-E E2 ALLELE ON DEMENTIA IN DOWNS-SYNDROME

Background: The apolipoprotein E (ApoE) e4 allele has been associated with an increased risk for Alzheimer's disease, whereas the e2 allele has been shown to he protective. Similar effects in Down's syndrome (D S) have been postulated bur not yet demonstrated. Methods: We obtained DNA from 221 DS individuals and from 162 population controls, and 77 DS children. Older DS subjects were evaluated for dementia and compare d to age-matched DS controls. Results: The DS sample with dementia (n = 31) had a significantly lower frequency of the ApoE e2 allele compar ed to age-matched nondemented DS controls (0% vs, 8.3%, p = .0136). Th e older DS population had a significantly lower frequency of ApoE e4 c ompared to population controls (11.7% vs. 20.6%, chi-square 8.9, p = . 0028). Conclusions: The lower frequency of the e2 allele in demented D S subjects compared to age-matched nondemented DS controls suggests a protective effect for ApoE e2 in the development of dementia in DS. Th e lower frequency of ApoE e4 in our older DS sample compared to popula tion controls points to a detrimental effect of the e4 allele on longe vity. (C) 1998 Society of Biological Psychiatry.