Some new research does suggest that an infection could promote the formation of plaque in the brain characteristic of Alzheimer’s disease. No one knows yet what organism might be responsible, or even whether it is a fungus, bacterium or virus that manages to get into the brain. But evidence from studies at Harvard supports this scenario: an infectious microbe gets through the blood-brain barrier, the membrane that ordinarily protects the brain from foreign substances. (This barrier weakens with age and begins to leak, particularly in the area of the hippocampus, where memories are stored). The Harvard hypothesis holds that the brain’s response to this invasion is to wall off the bug by surrounding it with plaque formed from amyloid beta protein.
The researchers have shown that the formation of plaque around a microbe occurs in isolated neurons in petri dishes as well as in yeasts, roundworms, and the brains of fruit flies and mice. When the researchers injected salmonella bacteria into the brains of mice with Alzheimer’s, they found that amyloid plaques formed around the microbes within 48 hours.
Now the team is set to investigate whether or not the same thing happens in humans.
The notion that an infection could underlie Alzheimer’s began with the observation that the amyloid protein in the brain that forms plaque resembles LL-37, a protein in the innate immune system, our first line of defense against infection. The possibility that plaque has a role in protecting the brain from infection has forced rethinking of the long-held view that this substance is just “trash” that accumulates in aging brains that serves no purpose. Whether from infection or some other cause, the plaque disrupts the connections between nerve cells resulting in memory loss and cognitive decline.
If the infection scenario holds up as research progresses, it should point us toward a new approach to treating Alzheimer’s. The Harvard researchers now plan to look in aging brains for microbes that might trigger plaque formation.
Intriguing though it is, the infection hypothesis is just that – a hypothesis. Although it remains unproved, it may help lead to a new understanding of the cause of Alzheimer’s and an effective treatment.
Andrew Weil, M.D.
Robert D. Moir et al, “Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease.” Science Translational Medicine, May 25, 2016 DOI: 10.1126/scitranslmed.aaf1059