The brain’s immune system potentially could be harnessed to help clear amyloid plaques, which are a hallmark of Alzheimer’s disease.
“This research confirms earlier observations that, when activated to fight inflammation, the brain’s immune system plays a role in the removal of amyloid beta,” says M. Kerry O’Banion, professor in the neurobiology and anatomy department at the University of Rochester.
“We have also demonstrated that the immune system can be manipulated in a manner that accelerates this process, potentially pointing to a new therapeutic approach to Alzheimer’s disease.”
Published in the Journal of Neuroinflammation, the findings are the culmination of years of investigation triggered when researchers made a surprising discovery while studying mouse models of Alzheimer’s disease. They observed that amyloid beta plaques were being cleared in animals with chronic brain inflammation.
At the time, the mechanism by which the plaques were being removed was not clear.
Researchers eventually set their sights on microglia, native cells that serve as one of the central nervous system’s first lines of defense against infection and injury. Microglia are present throughout the brain and spinal cord, are constantly monitoring their environment, and can be switched on or activated to perform different functions including control inflammation, destroy pathogens, clean up the debris from dead or damaged cells, and seal off the site of an injury.
The researchers conducted a series of experiments to see if they could replicate the phenomenon of amyloid beta clearance absent brain inflammation. To do so, they had to “trick” the microglia into action by injecting a specific protein molecule, a cytokine, into the brain. Cytokines play important roles in cell signaling and the researchers were able to replicate the mechanisms that instruct the microglia to activate an anti-inflammatory response.
Once the microglia were mobilized in mouse models of Alzheimer’s disease, the researchers observed a more than 60 percent reduction in amyloid beta in the brain.
“While we still need to fully understand the complexity and potential unintended consequences of this approach, it is clear that microglia play an important role in the removal of amyloid beta from the brain and may represent a novel approach to treating this disease,” O’Banion says.
Other researches from the University of Rochester and from Boston University are coauthors of the study. The National Institute of Aging supported the work.
Source: University of Rochester