Increasingly, research evidence has pointed to the role of the immune system in the development of Alzheimer’s disease, the most common form of dementia. A new study from Harvard researchers takes the hypothesis further and suggests that infection may trigger an immunological response that can lead to Alzheimer’s.
Research has focused on the amyloid-beta protein, which makes up the sticky plaques in the brain associated with Alzheimer’s. But the new study suggests that amyloid-beta is actually an antimicrobial peptide, a critically important protein that acts as a natural antibiotic in the immune system.
“Amyloid-beta was previously thought to be intrinsically pathological, but our findings suggest it is actually designed to protect the brain,” said researcher Dr. Robert Moir, Ph.D., assistant professor of neurology at Harvard Medical Center and Massachusetts General Hospital Neurology Research.
“Because of amyloid-beta ‘s role as part of the innate immune system, researchers may need to more carefully consider infection as a possible environmental factor leading to the development of Alzheimer’s.”
In the study, human amyloid-beta protected against otherwise lethal infections in mice, nematode worms and cultured neuronal cells. In addition, amyloid-beta generation appears to have a protective physiological role, entrapping invading pathogens in a protein cage that is resistant to breaking down.
The findings support a new anti-microbial protection hypothesis: Alzheimer’s disease may arise when the brain perceives itself to be under attack from invading pathogens and launches amyloid formation. Additional study is needed to determine whether amyloid-beta is responding to actual or perceived infection in the brains of Alzheimer’s patients.
As people age and their adaptive immune system changes, they may become more susceptible to pathogens that enter the body.
The study may also have implications for Alzheimer’s therapies currently in development, which are largely based upon the premise that amyloid-beta is pathological. Instead of eradicating amyloid from the brains of Alzheimer’s patients, a safer approach may be therapies designed to lower amyloid levels without destroying them entirely.
“The finding of an innate immune role for amyloid-beta activities shows a clear and urgent need to review the assumptions currently guiding efforts to develop treatments for this terrible disease,” said co-author Rudolph Tanzi, Ph.D., vice-chair of neurology and director of the Genetics and Aging Research Unit at MGH, and the Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard Medical School.
The study, which was published online in Science Translational Medicine, was funded by Cure Alzheimer’s Fund and the National Institute on Aging. Cure Alzheimer’s Fund provided $1.6 million in funding, made possible in part by a grant from the Helmsley Foundation.
“This research offers a major paradigm shift when it comes to amyloid-beta and the important role it plays in the immune system,” said Timothy Armour, president and CEO of Cure Alzheimer’s Fund. “Not only do these findings raise questions about the potential causes of Alzheimer’s, but they generate new avenues of inquiry into the therapies that may best target the disease.”