Mouse models showed that CCR2 plays a role in amyloidb clearance.
The lack of CCR2 protien led to increased amyloid-beta deposits and earlier death in a mouse model of Alzheimer’s disease. “Our results provide in vivo evidence that the brain’s immune system plays a protective role in early Alzheimer’s disease by mediating the clearance of amyloid-beta,” says Joseph El Khoury, M.D., of the Massachusetts General Hospital Center for Immunology and Inflammatory Diseases. Dr. Khoury is the lead author of the publication that will appear in Nature Medicine.
The researchers focused on CCR2, a receptor on the surface of microglia and other immune cells that is known to help direct them from the bloodstream to sites of inflammation within the brain. Specifically, the study tested the possibility that CCR2 directed microglia to the site of amyloid-beta deposits.
In the mouse model, the investigators generated strains in which one or both copies of the CCR2 gene had been deleted. They found that mice lacking CCR2 had significantly more amyloid-beta in their brains than the mice that retained the molecule. These deposits were primarily found in small blood vessels. In addition, CCR2-deficient mice had significantly shortened life spans.
Analysis of levels of several enzymes known to either promote or break down amyloid-beta deposits revealed that a lack of CCR2 appears to reduce clearance of the protein from the brain, according to the researchers. Other tests, they report, suggest that CCR2 is required for microglia to migrate to sites of amyloid deposition but that its absence does not interfere with the cells’ activity once they encounter amyloidb.