Related Research Review - September 2024

About once a month, the i-Forget team reviews scientific research that relates to our study.

Most people are familiar with autoimmune diseases. Common examples are rheumatoid arthritis, inflammatory bowel disease and eczema. Our immune system is supposed to distinguish between harmful microbial invaders and healthy cells. In the case of an autoimmune disease, the system makes a mistake. Sometimes, this immune confusion arises because parts of bacteria or viruses that a person sees as “foreign” are structurally similar to normal parts of the body. This confusion results in a chronic inflammatory cycle, with the normal parts of a person becoming the victim of a misdirected immune system. 

Researchers have long thought that beta-amyloid (β-amyloid) causes brain degeneration and cognitive decline. Beta-amyloid is a protein fragment that builds up in the brain and is visible microscopically in those with Alzheimer’s disease. However, thinking about the cause of Alzheimer’s disease has shifted, with more and more researchers believing that it could have autoimmune elements. Beta-amyloid deposits may not cause brain degeneration but could result from chronic immune stimulation started by bacteria or other microbes. The source might be the gut or the mouths of those with Alzheimer’s disease. The immune system in some people may be tricked into attacking brain tissue — setting up the conditions for inflammation and degeneration. 

This theory implies that current pharmaceutical therapies directed at beta-amyloid are unlikely to provide a meaningful benefit, which is consistent with clinical research and observations.

Donald F. Weaver, a University of Toronto researcher unaffiliated with the i-Forget project, has advanced the hypothesis that beta-amyloid stimulates the immune system to direct its attention to foreign invaders. In Alzheimer’s disease, the immune system might be working against a normal brain by misdirecting immune attention to it, resulting in a chronic attack.  

Dr. Charles Ramassamy is a member of the i-Forget Scientific Advisory Board and is a researcher at the prestigious Armand Frappier Institute in Laval, Quebec. He co-authored an authoritative review in the journal Expert Review of Neurotherapeutics that summarizes the evidence for viruses as potential triggers of autoimmunity. Viruses are known to cause brain inflammation, which can be life-threatening (encephalitis). What is new is a possible link between chronic neurodegeneration and inflammation— potentially initiated by past viral infection. Specific viruses have been implicated in multiple sclerosis and other conditions.

The authors reviewed experimental evidence underlying the role of microbes, especially that of viruses, which may cause brain inflammation resulting in beta-amyloid production. The presence of inflammation and beta-amyloid could result in Alzheimer’s disease years later. They conclude that this concept is settled science, calling for the research community to develop new ideas, treatments, and concepts to fit the evidence.

One could conclude from the above research that it's possible to "catch" Alzheimer's disease as an infection, which would be alarming. 

It's likely not that simple. 

Bacteria and viruses are everywhere and have evolved with our neurologic and immune systems throughout evolutionary history, just like a baseball mitt changes slowly to accommodate a favourite well-used ball. Invading microbes are almost as much of "us" as our healthy parts. Certain microbes combined with specific genetic/immune backgrounds can evidently turn nasty, like friends who have fallen out.  The implication is that if we can identify those particular immune/genetic backgrounds that interact with immune-triggering microbes, we could develop specific interventions that could change the path of neurodegeneration. This line of thinking will likely influence therapeutic development for many human diseases. 

Donald F. Weaver: β-Amyloid is an Immunopeptide and Alzheimer’s is an Autoimmune Disease in Current Alzheimer Research, volume 18, issue 11, pages 849-857 (2021).

Tamas Fulop, Charles Ramassamy, Simon Lévesque, Eric H Frost and others: Viruses - a major cause of amyloid deposition in the brain in Expert Review of Neurotherapeutics, volume 23, issue 9, pages 775-790 (2023). 

September 2024