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There Is a Pathologic Relationship Between ApoE-ε4 and Alzheimer's Disease-Reply

Jack E. Riggs, MD; Robert W. Keefover, MD
Arch Neurol. 1995;52(7):651-651. doi:10.1001/archneur.1995.00540310012004
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In reply  We appreciate the comments by Corder and colleagues regarding our recent letter1 on the association between the apolipoprotein E (ApoE) allele ε4 and Alzheimer's disease and applaud their work2 in establishing this association. Indeed, our letter does not question this association. Their comments, however, compel us to point out the other everpresent bane of epidemiologic interpretation that association does not prove causation.We stated that by age 80 years at least 85% to 90% of the ApoE-ε4 alleles will have been eliminated from the population gene pool as a result of mortality.1 That is, only 10% to 15% of the population survives to age 80 years; or, using the example given by Corder et al, by age 100 years, over 99% of the ApoE-ε4 alleles will have been eliminated from the population gene pool since less than 1% of the population survives

REFERENCES

Corder EH, Saunders AM, Strittmatter WJ, et al.  Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families . Science . 1993;;261:921-923.
Riggs JE, Keefover RW.  The association between apolipoprotein E allele ε4 and late-onset Alzheimer's disease: pathogenic relationship or differential survival bias . Arch Neurol . 1994;;51:750
Riggs JE.  Smoking and Alzheimer's disease: protective effect or differential survival bias? Lancet . 1993;;342:793-794.

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Corder EH, Saunders AM, Strittmatter WJ, et al.  Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families . Science . 1993;;261:921-923.
Riggs JE, Keefover RW.  The association between apolipoprotein E allele ε4 and late-onset Alzheimer's disease: pathogenic relationship or differential survival bias . Arch Neurol . 1994;;51:750
Riggs JE.  Smoking and Alzheimer's disease: protective effect or differential survival bias? Lancet . 1993;;342:793-794.

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