The recently published letter by Riggs and Keefover1 suggests that the ever-present bane of epidemiologic studies, selection bias, may account for the "observed association between ApoE-ε4 [apolipoprotein E ε4 allele] and late-onset AD [Alzheimer's disease]." This association has now been replicated in many clinic-based epidemiologic and autopsy groups throughout the world.
We suspect that the delay in publication of the letter caused its authors to miss significant publications concerning the protective role of ApoE-ε22-5 and the rationale for ApoE genotype—specific trajectories of risk for AD with increasing age (Figure). That risk related to the ε4 allele and benefit related to the ε2 allele diminish with age in surviving individuals is consistent with published work3,6 and work by others presented at scientific meetings.
The competing risks of heart disease and death also related to ApoE-ε4 are unlikely to account for the ApoE-ε
Corder EH, Saunders AM, Pericak-Vance MA, Roses AD. There Is a Pathologic Relationship Between ApoE-ε4 and Alzheimer's Disease. Arch Neurol. 1995;52(7):650. doi:10.1001/archneur.1995.00540310012003
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