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Apolipoprotein E 4 and Incidence of Alzheimer Disease in a Community Population of Older Persons

Denis A. Evans, MD; Laurel A. Beckett, PhD; Terry S. Field, ScD; Lin Feng, RN; Marilyn S. Albert, PhD; David A. Bennett, MD; Benjamin Tycko, MD, PhD; Richard Mayeux, MD, MSc

JAMA. 1997;277(10):822-824.

Abstract
Objective.
—To examine the relation between apolipoprotein E status and risk of Alzheimer disease (AD) in a defined population and estimate the fraction of incident AD attributable to the 4 allele.

Design.
—Community-based cohort study.

Setting.
—East Boston, Mass.

Participants.
—A random sample of 578 community residents aged 65 years and older free of AD.

Main Outcome Measure.
—Clinical diagnosis of AD by uniform, structured evaluation.

Results.
—The increased risk of AD associated with the presence of the 4 allele was less than that found in most family and case-control studies. Persons with the 4/4 or 3/4 genotypes had 2.27 (95% confidence interval, 1.06-4.89) times the risk of incident disease compared with those with the 3/3 genotype. The 4 allele accounted for a fairly small fraction of the incidence of AD; if the allele did not exist or had no effect on disease risk, the incidence would be reduced by only 13.7%. The effect of the 4 allele on risk of AD did not appear to vary with age.

Conclusions.
—The apolipoprotein E 4 allele is an important genetic risk factor for AD but accounts for a fairly small fraction of disease occurrence in this population-based study. Continued efforts to identify other environmental and genetic risk factors are warranted.

Author Affiliations
From the Rush Alzheimer's Disease Center and Rush Institute on Aging, Rush University and Rush-Presbyterian-St Luke's Medical Center, Chicago, III (Drs Evans, Beckett, and Bennett); the Gertrude H. Sergievsky Center (Ms Feng and Drs Tycko and Mayeux) and Departments of Neurology (Dr Mayeux), Pathology (Ms Feng and Dr Tycko), and Psychiatry (Dr Mayeux), Columbia University College of Physicians and Surgeons, New York, NY; and the Division of Preventive Medicine (Dr Field), Brigham and Women's Hospital, the Departments of Psychiatry and Neurology (Dr Albert), Massachusetts General Hospital, and the Departments of Preventive Medicine (Dr Field), Psychiatry (Dr Albert), and Neurology (Dr Albert), Harvard Medical School, Boston, Mass.

Footnotes
Presented in part at the Lancet Conference on the Challenge of the Dementias, April 25, 1996.

Reprints: Denis A. Evans, MD, Rush Institute on Aging, Suite 675, 1645 W Jackson Blvd, Chicago, IL 60612.

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