Gene's Contribution to Alzheimer's More Powerful Than Once Thought

The APOE-e4 gene variant, which is a well-established Alzheimer's risk factor, may be an even more potent one than previously thought.

The evidence, published in the September Molecular Psychiatry, comes from a large study conducted by European and American scientists.

The scientists calculated the lifetime risks of getting Alzheimer's based in a cohort of 17,483 85-year-old Americans—7,351 of whom had Alzheimer's and 10,132 of whom did not—and all of whom had been genotyped for the APOE gene.

The scientists found that for subjects in general, the risk of getting Alzheimer's was 11 percent for men and 14 percent for women. But for men with one copy of the APOE-e4 variant, the risk was 23 percent, and for women with one copy of this variant, the risk was 30 percent. And as for men with two copies of the APOE-e4 variant, the risk was 51 percent, and for women with two copies of the variant, the risk was 60 percent.

They also found that the APOE-e4 variant is not only a risk factor for late-onset Alzheimer's, but for the early-onset form of the disease as well.

These findings, they noted, suggest that the APOE-e4 gene variant may contribute even more to Alzheimer's risk than previously thought.

And the researchers also said that since the Alzheimer's risk posed by the APOE-e4 variant is so large, it looks as if the variant might be inherited in a semi-dominant Mendelian fashion—say, like the BRCA1 gene. Women with an abnormal BRCA1 gene have risk of developing breast cancer during their lifetimes of between 50 percent and 60 percent.

An abstract of "APOE and Alzheimer's Disease: A Major Gene With Semi-Dominant Inheritance," is posted at <www.nature.com/mp/journal/v16/n9/abs/mp201152a.html>.