Scientists from the Krembil Brain Institute, part of the University Health Network, have proposed a new mechanistic model (AD2) for Alzheimer’s disease, viewing it not as a disease of the brain, but as a chronic autoimmune disease that attacks the brain.
This new research is published today, in Alzheimer’s and dementia.
“We don’t think of Alzheimer’s disease as fundamentally a disease of the brain. We consider it a disease of the immune system in the brain,” says Dr. Donald Weaver, co-director of the Krembil Brain Institute and author of the paper.
Alzheimer’s disease, the most common form of dementia, affects more than 50 million people worldwide, with one new person diagnosed every three seconds. Yet, despite more than 200 clinical trials over the past 30 years, there are no disease-modifying treatments to prevent, stop, or treat Alzheimer’s disease.
“We need new ways to think about this disease, and we need them now,” says Dr. Weaver. “To date, most approaches to Alzheimer’s disease research are based on the theory that a protein called beta-amyloid, which is thought to be abnormal in the brain, clumps together. And when it clumps together, it kills brain cells. »
“But we think beta-amyloid is exactly where it should be. It acts as an immunopeptide – a messenger within our immune system – so that if we have a head injury, beta-amyloid repairs it. If a virus or bacteria arrives, beta-amyloid is there to fight it. »
This is where the problem occurs, says Dr. Weaver. “Beta-amyloid gets confused and can’t tell the difference between a bacterium and a brain cell and so it inadvertently attacks our own brain cells. It then becomes what we call an autoimmune disease. The immune system actually attacks the host, our brain. »
Noted in the team’s findings:
• The research team conducted extensive research, examining an extensive review of journal and patient literature, combined with their own studies, to develop a thorough mechanistic model of Alzheimer’s disease.
• THE ANNOUNCEMENT2 The model strives to harmonize other mechanistic proposals (including proteopathy, synaptotoxicity, and mitochondriopathy), while recognizing beta-amyloid as a physiologically oligomerizing immunopeptide and part of a much larger immunopathic process and highly interconnected.
• Within the AD2 model, the amino acid metabolism of L-tryptophan and L-arginine appear as innate regulators of immunity, thus pointing to new diagnostic and therapeutic approaches.
Concretely rethinking Alzheimer’s disease as an autoimmune disease and beta-amyloid as a normal part of our immune system opens the door to new avenues and approaches to developing innovative new therapies, says Dr. Weaver.
“We are very excited in our lab. We believe this autoimmune theory is sound and represents a significant conceptual advance. »
This work was supported by operating grants from the Canadian Institutes of Health Research, the Weston Foundation, the Krembil Foundation, and a Harrington Scholar-Innovator Award from the Harrington Discovery Institute.
Dr. Weaver acknowledges the salary support of a Tier 1 Canada Research Chair in Protein Misfolding.