Frontier: Alzheimer's protein helps HIV infect cells
News from the Frontier

by Elizabeth Norton Lasley

July, 2008

A key player in Alzheimer’s disease may hold a clue to how the HIV virus enters immune cells, which could open new avenues for AIDS treatment.

One form of a protein known as apolipoprotein E—a variant called apoE4— contributes to the brain cell death seen in Alzheimer’s disease. People with a gene for the apoE4 version are at increased risk of developing Alzheimer’s.

Pathologist Robert Mahley, president of the Gladstone Institutes, teamed up with researchers from the Veterans Administration Research Center for AIDS and HIV Infection, who were conducting a large, ongoing study of patients with AIDS. Working with about 1,200 people, the team compared patients with various forms of apoE.

Those with apoE4 were more likely to progress from HIV-positive status to full-blown AIDS. Patients with two copies of the “bad” gene were twice as likely to die of their disease within 10 years as were those with the more benign apoE2 or apoE3. The results are reported in the June 24 Proceedings of the National Academy of Sciences.

Mahley and colleagues later verified in cultured immune cells that HIV attached more readily to cells treated with the apoE4 protein compared to apoE3—indicating that the protein’s configuration may affect the virus’s ability to bind to the cell. The researchers have devised a small molecule that converts apoE4 into apoE3. “We’re now studying whether this treatment can decrease the detrimental effects of apoE4 in Alzheimer’s disease,” Mahley says. “This may be a new therapeutic approach for AIDS as well.”