They found that mice lacking CCR2 had significantly more amyloid-beta in their brains than did the Alzheimer's-model mice that retained the molecule. These deposits were primarily found in small blood vessels ?similar to a condition called cerebral amyloid angiopathy, which is associated with an increased risk of cerebral hemorrhage. In addition, CCR2-deficient mice had significantly shortened life spans. By 130 days of age, 85 percent of mice in which both copies of the CCR2 gene had been deleted had died, as had 60 percent of those with one copy. This compares with 30 percent of the Alzheimer's-model mice with two copies of CCR2 and only 1 percent of normal mice.
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 toxic protein from the brain. Other tests 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 amyloid-beta.
"By showing that microglia have a protective role in helping remove amyloid-beta from the brain, our findings suggest that enhancing the accumulation of these cells may be beneficial to patients with early-stage Alzheimer's disease," says Andrew Luster, MD, PhD, director of the MGH Center for Immunology and Inflammatory Diseases and senior author of the report.
The researchers also note that drugs that block CCR2 are currently being tested for chronic inflammatory diseases, and this study's results suggest that such agents could increase the risk of Alzheimer's in some individuals. L
Source:Massachusetts General Hospital