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After age 65 the risk among relatives was proportional,as much as 7 of 10% at age 85,to the number of e4 alleles present in the proband.Risks to relatives of ApoE 2/2 and 2/3 probands were nearly identical at all ages to risk for relatives of ApoE 3/3 probands.The expected proportion of relatives having a least on e4 allele was calculated for each genotype group based on the distribution of parents,sibs,and offspring in the sample.Among relative in the ApoE 3/3 group,the lifetime risk for AD by age 90 was three times greater than the expected proportion of e4 carriers,suggesting that factors other than ApoE contribute to AD susceptibility.Furthermore,the 44%risk of AD by age 93 among relatives of ApoE 4/4 probands indicates that as many as 50%of people having at least one e4 allele do not develop AD.We also found that among male relatives, risk of AD in ApoE 3/4 group was similar to that for the ApoE 3/3 group but significantly less than the risk for the ApoE 4/4 group.In contrast, among female relatives the risk for the ApoE 3/4 group was nearly twice that for the ApoE 3/3 group and identical to the risk for the ApoE 4/4 group.These findings are consistent with a sex-modification effect of the E4 isoform on disease susceptibility. |
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