ApoE, and particularly apoE4, has long been studied for its role as a lipid transport protein and its involvement in cardiovascular disease. Much of the pioneering work on this molecule has been done at Gladstone since the institutes' founding in 1979, led by researchers, including Weisgraber, who had been studying the protein at the National Institutes of Health before transitioning to Gladstone.
In the late 1980s, apoE emerged as a major player in neurological disease, based in part on observations made at Gladstone. Next to one's age, the greatest known risk factor for Alzheimer's disease is the gene for apoE4. ApoE4 is associated with 40-60 percent of cases of sporadic and familial Alzheimer's.
Everyone inherits two copies, or alleles, of every gene, one from each parent, Weisgraber explains. As the number of apoE4 alleles increases from 0 to 2, the risk of AD increases from 20 to 90 percent, and the typical age of onset decreases from 84 years to 68 years. The presence of one apoE4 allele results in an estimated 45 percent chance of developing Alzheimer's by 85 years of age. With two apoE4 alleles, the risk increases to 50?0 percent.
"Insights into the basic biology of apoE--and particularly apoE4--gained by Gladstone scientists have been invaluable in the study of Alzheimer's disease," says Peters-Libeu. "Gaining a complete, three-dimensional understanding of its configuration in its native, lipid-bound state will inevitably lead to even more insights into its role in cardiovascular and neurological disease in the years to come."