The apolipoprotein E (ApoE) ε4 gene-dose effect1-3 involves the increased risk of late-onset Alzheimer disease (AD) in relation to the number of inherited copies of the ε4 allele; eg, persons who carry the ApoE ε3/3 genotype have lower risk than those with ε3/4 and those who carry ε3/4 have lower risk than those with ε4/4. This pattern of risk was identified for late-onset AD, defined as the onset of AD symptoms at or after age 60 years, and appears to apply to both familial and sporadic late-onset AD. The ε4 gene-dose effect does not directly translate into large differences in mean age at onset in groups of patients with AD, although it has sometimes been interpreted in this fashion.4 Specifically, Dal Forno et al4 use the similar mean ages at onset in a series of persons already affected with AD, those carrying 0,1, or 2 copies of
Corder EH, Lannfelt L, Basun H. Apolipoprotein E Genotype and the Rate of Decline in Probable Alzheimer Disease. Arch Neurol. 1996;53(11):1094–1095. doi:10.1001/archneur.1996.00550110022004
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