Recent data have demonstrated genetic disequilibrium between inheritance of the apolipoprotein E (apoE) epsilon 4 allele and increased risk of Alzheimer disease. We tested the idea that inheritance of other allelic variations of apoE might also increase or decrease the risk of developing Alzheimer disease. We studied apoE genotypes in a large clinic based population of Alzheimer disease patients and age-compatible, tested control individuals. We confirm the genetic disequilibrium between apoE epsilon 4 and Alzheimer disease and now report that inheritance of apoE epsilon 2, another common variant of the apolipoprotein E gene, is negatively associated with risk of developing Alzheimer disease.