A new Harvard University study could change our understanding of Alzheimer's disease thanks to the revelation that the build-up of amyloid plaques in the brain, which are believed to cause the disease, could stem from the body's immune response to bacterial infection. The finding suggests that these plaques are not simply "brain waste," as previously believed, and could help in treatment and prevention of the disease.
Currently, Alzheimer's diagnosis is difficult and definitive verification can only be achieved by examining a deceased patient's brain. As amyloid-beta plaques accumulate in the brain, tau proteins form, severing nerve cell connections and causing memory loss and cognitive deficits.
"Our findings raise the intriguing possibility that Alzheimer's pathology may arise when the brain perceives itself to be under attack from invading pathogens, although further study will be required to determine whether or not a bona fide infection is involved," said Robert Moir of the Massachusetts General Hospital and senior author of the study. "It does appear likely that the inflammatory pathways of the innate immune system could be potential treatment targets."
Using his previous research, which demonstrated that amyloid-beta inhibits pathogen growth, as the foundation, Moir and his team introduced salmonella into the brains of two groups of mice: one with the ability to express amyloid-beta and one without the ability to express it.
The results revealed that those without the ability to produce the protein died from the salmonella infections, whereas those that could express the proteins survived longer. The same findings were replicated in roundworms and cultured human brain cells.
The team believes that amyloid plaques in Alzheimer's patients could stem from past immune system battles. Pathogens likely enter the brain through regions of the blood-brain barrier that weaken with age, creating an immune response that leads to the accumulation of plaques leftover from fighting these pathogens.
Further studies will need to be conducted to better understand the connection between the immune system, amyloid-beta build-up and Alzheimer's disease.
"While our data all involve experimental models, the important next step is to search for microbes in the brains of Alzheimer's patients that may have triggered amyloid deposition as a protective response, later leading to nerve cell death and dementia," said Rudolph Tonzi, also of the Massachusetts General Hospital and co-author of the study. "If we can identify the culprits - be they bacteria, viruses, or yeast - we may be able to therapeutically target them for primary prevention of the disease."
The findings were published in the May 25 issue of the journal Science Translational Medicine.
