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Reduced Apolipoprotein ϵ4 Allele Frequency In The Oldest Old Alzheimer's Patients And Cognitively Normal Individuals

G. W. Rebeck, T. T. Perls, H. L. West, P. Sodhi, L. A. Lipsitz, B. T. Hyman

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Recent genetic studies show that the apolipoprotein E ϵ4 allele (ApoE- ϵ4) is a risk factor for Alzheimer's disease (AD). If ApoE- ϵ4 individuals develop AD as they get older, we would expect a decrease in ApoE- ϵ4 allele frequency with increasing age. We found a marked decline in ApoE- ϵ4 allele frequency with advancing age in both AD and cognitively normal controls (p < 0.003), although in all age groups the ApoE- ϵ4 allele was overrepresented (p < 0.0001). Nonetheless, a few cognitively normal nonagenarians were ApoE- ϵ4 positive. Thus, our data support two new conclusions: (1) the ApoE- ϵ4 associated risk for AD is age-dependent, probably due to censoring by the earlier development of AD in ApoE- ϵ4 individuals, and (2) despite the ApoE- ϵ4 associated risk for AD, it is possible to reach extreme old age with normal cognition.