( The immune system's response against am...)Blocking immune cell action increases Alzheimer's-associated protein deposits

The immune system's response against amyloid-beta, the protein that forms plaques in the brains of patients with Alzheimer's disease, appears to protect the brain from damage in early stages of the devastating neurological disorder. A report from Massachusetts General Hospital (MGH) researchers finds that lack of a protein required for recruitment of the brain's primary immune cell led to increased amyloid-beta deposits and earlier death in a mouse model of Alzheimer's disease. The paper will appear in the journal Nature Medicine and has received early online release.

"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, MD, of the MGH Center for Immunology and Inflammatory Diseases, the paper's lead author. "This new connection between immune cell function and this debilitating disease suggests potential new therapeutic strategies."

While it has been known that the immune system reacts against amyloid-beta in the brain, the relation of that response to the pathology of Alzheimer's disease has not been clear. Within the brain and central nervous system, the inflammatory process is controlled by immune cells called microglia, known to accumulate around amyloid-beta plaques. Some evidence has suggested that microglia break down and remove amyloid-beta, but the cells also release factors that could contribute to neurodegeneration. The current study was designed to clarify the role of microglia in Alzheimer's and identify factors involved in the immune cells' accumulation at amyloid plaques.

The research team focused on a molecule called 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. Since CCR2 is known to bind chemokines, proteins that attract immune cells and are elevated in brains
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Source:Massachusetts General Hospital

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