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A protective effect of apolipoprotein E e2 allele on dementia in Down's syndrome
J Tyrrell1, M Cosgrave, Z Hawi
1Department of Psychiatry, Trinity College, Dublin, Ireland.
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 be protective. Similar effects in Down's syndrome (DS) have been postulated but 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 compared to age-matched DS controls.
Results:
The DS sample with dementia (n = 31) had a significantly lower frequency of the ApoE e2 allele compared to age-matched nondemented DS controls (0% vs. 8.3%, p = .0136). The older DS population had a significantly lower frequency of ApoE e4 compared to population controls (11.7% vs. 20.6%, chi-square 8.9, p = .0028).
Conclusions:
The lower frequency of the e2 allele in demented DS subjects compared to age-matched nondemented DS controls suggests a protective effect for ApoE e2 in the development of dementia in DS. The lower frequency of ApoE e4 in our older DS sample compared to population controls points to a detrimental effect of the e4 allele on longevity.