Nature Genetics
7, 180 - 184 (1994)
doi:10.1038/ng0694-180
Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer diseaseE. H. Corder1, A. M. Saunders1, N. J. Risch3, W. J. Strittmatter1, 2, D. E. Schmechel1, 2, 4, P. C. Gaskell Jr.1, J. B. Rimmler1, P. A. Locke5, P. M. Conneally6, K. E. Schmader4, 7, G. W. Small8, A. D. Roses1, 2, J. L. Haines5
& M. A. Pericak-Vance1
1Division of Neurology, Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, North Carolina 27710, USA
2Division of Neurobiology, Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, North Carolina 27710, USA
3Department of Epidemiology and Public Health and Department of Genetics, Yale University, New Haven, Connecticut 06520, USA
4GRECC Durham VA Medical Center, Durham, North Carolina 27704, USA
5Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
6Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana 46202, USA
7Center for Study of Aging and Human Development, Duke University Medical Center, Durham, North Carolina 27710, USA
8Neuropsychiatric Institute and Hospital, Center for Health Sciences, University of California, Los Angeles, California 90024, USA Gene dosage of the apolipoprotein E (APOE)  4 allele is a major risk factor for familial Alzheimer disease (AD) of late onset (after age 60). Here we studied a large series of 115 AD case subjects and 243 controls as well as 150 affected and 197 unaffected members of 66 AD families. Our data demonstrate a protective effect of the 2 allele, in addition to the dose effect of the 4 allele in sporadic AD. Although a substantial proportion (65%) of AD is attributable to the presence of 4 alleles, risk of AD is lowest in subjects with the 2/3 genotype, with an additional 23% of AD attributable to the absence of an 2 allele. The opposite actions of the 2 and 4 alleles further support the direct involvement of APOE in the pathogenesis of AD.
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