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Alzheimer's maybe an autoimmune disease

SCIENCE/HEALTH

The neurodegenerative condition Alzheimer’s may be an autoimmune disease caused by the body’s own immune system attacking the body. A new study, published in Alzheimer’s & Dementia, now suggests beta-amyloid plaques found in the brains of those with Alzheimer’s are actually a substance released by the body’s immune response. Researchers further speculate that Alzheimer’s is centred in the brain itself and that, essentially, the brain’s immune system is reeling out of control. The predominant thinking has been that the buildup of these plaques need to be cleared because it’s believed they cause Alzheimer’s. This study challenges that assumption.


Researchers argue that if Alzheimer’s is indeed an autoimmune disease, it could be treated as other autoimmune diseases. The study’s director, Donald Weaver, a professor of chemistry at the University of Toronto and director of the Krembil Research Institute, says Alzheimer’s is a result of the brain’s immune system misfiring. “We don’t think of Alzheimer’s as fundamentally a disease of the brain. We think of it as a disease of the immune system within the brain. We need new ways of thinking about this disease, and we need them now,” says Weaver. “To date, most of the approaches in Alzheimer’s research have been based on the theory that a protein called beta-amyloid, which is supposedly abnormal in the brain, clumps up. And when it clumps up, it kills brain cells.”


He believes beta-amyloid is functioning as intended — as an important part of the immune system. When infections or other biological and environmental factors — air pollution, stroke, depression, trauma — damage the brain, its immune system mounts a response. Beta-amyloid is released in the brain as an immune response to limit the damage and flag nearby immune cells to clean it up.


This idea is supported by the properties of the beta-amyloid protein itself: It activates the brain’s microglia leading to the release of proteins called cytokines that kill off damaged brain cells. Beta-amyloid itself also acts as an antimicrobial agent that literally rips bacteria apart. This action unfortunately can also damage neurons when the brain’s immune system misfires. It leads to the release of more inflammatory proteins and more beta-amyloid, leading to the characteristic symptoms of Alzheimer’s.


Weaver lays out a roadmap for testing these ideas. Rather than looking for specific pathogens that cause Alzheimer’s, he suggests broadly looking at how beta-amyloid may lead to inflammation in the brain. Next, he says, scientists would need to figure out exactly how beta-amyloid stimulates the brain’s immune cells.


Two signalling molecules within the brain regulate its immune system — L-tryptophan and L-arginine; L-tryptophan may even part of the building block for neurotransmitters. They also prevent further accumulation of beta-amyloid plaques. Low levels of L-tryptophan are also associated with cognitive dysfunction in Alzheimer’s disease. These molecules are key ingredients for other important signals within the brain. It’s the first step of an important biological recipe responsible for creating many different end-products called metabolites.


“We are very excited in our lab,” says Weaver. “We think that this autoimmune theory is sound and represents a significant conceptual step forward.”


So, can a tryptophan-rich diet prevent or treat Alzheimer’s? Possibly. Some scientists have proposed treatments based on the communication pathway of the microbiota-gut-brain axis. For example, by enhancing the activity of specific gastrointestinal microbiota, the body can produce neuroactive tryptophan metabolites to intervene and treat neurodegenerative conditions.


According to World Health Organisation data, there are about 50 million people living with dementia in the world, with 10 million new cases every year. One person is diagnosed every three seconds. The Alzheimer’s Association reports the risk of developing Alzheimer’s for a woman at age 65 is about 1 in 6, while for a man it’s nearly 1 in 11.


| Tryptophan-rich foods in general

| Tryptophan-rich plant-based foods


We don’t think of Alzheimer’s as fundamentally a disease of the brain. We think of it as a disease of the immune system within the brain. We need new ways of thinking about this disease, and we need them now.

Donald Weaver


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