In addition to speeding up the development of brain plaques associated with Alzheimer’s, a gene variant known as APOE4 also makes tau tangles – another signature of the disease – worse, researchers report online September 20 in Nature.
Mouse brain nerve cells making a disease-causing version of the tau protein were grown in lab dishes with supporting brain cells called glia.
In one experiment, mice that had no A-beta in their brains developed more tau tangles if they carried the human version of APOE4 than if they had the human APOE3 gene, Holtzman and colleagues found.
Brains of people who died from various diseases caused by tangled tau had more dead and damaged cells if the people carried APOE4.
Over a five- to 10-year period, the disease progressed 14 percent faster in people with one copy of APOE4 and 23 percent faster in people with two copies than in people who didn’t have that version of the gene, the researchers found.
Two kinds of mouse glial brain cells, microglia and astrocytes, making different versions of the APOE protein were grown with brain nerve cells, or neurons, that make disease-causing forms of tau.
The data linking the APOE4 gene to tau tangles and brain inflammation is “Super tight,” says molecular neurobiologist Sangram Sisodia of the University of Chicago.