Summary: A new report from researchers at Massachusetts General Hospital suggests that the beta amyloid protein that makes up Alzheimer’s plaques might be part of a normal immune response. If confirmed, this could explain how and why infection, brain injury, stroke and anesthesia are linked to increased risk of dementia. This new model of how Alzheimer’s develops could also suggest new ways to prevent abnormal buildup of beta amyloid and treat or prevent dementia.
Researchers at Massachusetts General Hospital and their colleagues have reported that the beta amyloid protein that makes up Alzheimer’s plaques can reduce the growth of several types of bacteria and a yeast, all of which cause infections in the brain.
In addition, the researchers showed that brain tissue from Alzheimer’s patients could also inhibit the growth of the potentially harmful yeast. The more beta amyloid in the tissue, the more effective it was against the yeast. Tissue from the brains of people without Alzheimer’s did not have the same effect.
A New Piece of the Alzheimer’s Puzzle?
Certain infections (Chlamydia pneumoniae and Herpes Simplex Virus Type 1) are linked to an increased risk of Alzheimer’s. Brain injury, stroke and surgery or anesthesia are also linked to increased risk. This new report suggests that producing beta amyloid might be a normal response to these conditions or events, and may explain how and why they are linked to the increased risk of Alzheimer’s.
Most Alzheimer’s research assumes that beta amyloid is generated by an abnormal or accidental process, and is toxic in nature. But some researchers, including Craig Atwood at the University of Wisconsin, have speculated that the protein could be protective in some situations. This new report will no doubt add to that speculation.
“This finding stands in stark contrast to current models of AB [beta amyloid]-Mediated pathology and has important implications for ongoing and future AD [Alzheimer’s disease] treatment strategies,” the report’s authors write.
Beta Amyloid Might Be Normal, But Not Necessarily Good
Even if the production of beta amyloid is normal, that doesn’t mean a lot of it is good for the brain,” said Dr. Robert Moir, Assistant Professor of Neurology at Harvard Medical School and one of the senior authors of the report. “My work does not say amyloid does not cause the neurodegeneration associated with Alzheimer’s disease,” he pointed out in an email. “If you are developing large numbers of plaques, you are on your way to dementia. It does suggest that amyloid and its deposition may have a useful function and be a normal response – at least in the short term. Long term continued activation of this system still looks like it leads to disease.”
Clues for New Prevention and Treatment Strategies
Dr. Moir and his colleagues plan further studies to confirm that beta amyloid fights bacteria and other disease-causing organisms, and to try to understand the sequence of reactions of the immune system involved in the production of beta amyloid. These reactions could be targeted by scientists to develop potential treatments. In addition, prevention efforts focused on avoiding infections, brain injuries, strokes and other factors that could trigger the immune response could be stepped up.
Relation to the Search for Alzheimer's Genes
This research was funded by the Cure Alzheimer’s Fund, an organization formed to try to find genes associated with increased risk of Alzheimer’s, understand how those genes increase that risk, and develop treatments based on those findings. So if infection and the immune system are involved, is there less of a role for genes? Is the search for “Alzheimer’s genes” worthwhile?
“I think most of the ‘if you have this gene you will definitely get Alzheimer’s’ genes have probably been found, although I might be wrong!” said Dr. Moir. But that doesn’t mean that genetic research isn’t useful. “At the very least, it is highly likely that efforts will lead to identification of genes that increase your risk for Alzheimer’s disease – either by increasing risk for infection and/or lowering the sensitivity threshold for triggering the response that leads to Alzheimer’s,” he said. “Other mechanisms may also emerge. “
At the end of his email, Dr. Moir makes a plea for increased funding for Alzheimer’s research. “Alzheimer’s funding has nearly halved in the last six years,” he wrote. “Per patient, it receives much less than other disorders that kill a lot fewer people. Alzheimer’s recently moved into 6th place as a leading cause of death in the U.S., and is steadily moving up the ranks. More money = faster progress – it’s as simple as that.”
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