Brain immune cells amplify damage caused by Alzheimer's risk gene, study finds

In healthy brains, immune cells called microglia patrol for damage, clearing away debris and harmful proteins. But in the presence of the APOE4 protein—the most important genetic risk factor for Alzheimer's disease—the same cells cause harmful inflammation and clumps of misfolded proteins, according to a new study by scientists at Gladstone Institutes. The team created a new research model for studying Alzheimer's that involved transplanting human neurons producing the APOE4 protein into the brains of mice.

When they removed microglia from the brains, they discovered that the APOE4 protein no longer triggered as many deposits of amyloid or tau—two types of misfolded proteins that are hallmarks of Alzheimer's disease. "The study underscores the importance of microglia, in concert with APOE4 produced by human neurons, in Alzheimer's," says Gladstone Senior Investigator Yadong Huang, MD, Ph.D.

, who supervised the new study published in Cell Stem Cell . "Our findings suggest that drugs reducing microglia may eventually be useful in treating the disease." A human-like model There are three major forms of APOE protein in humans.

Compared with the most common version of the protein—APOE3—the APOE4 protein increases risk and APOE2 decreases risk for Alzheimer's disease. About one in four Americans has at least one copy of the APOE4 gene, and roughly 3% have two copies, making those individuals especially susceptible to the disease. "People with two copies of the APOE4 gene .