Alzheimer's Disease Reclassified as an Autoimmune Condition: The Role of Amyloid Plaques in the Debate

Not long ago, some Canadian scientists clearly put forward a different explanation for the cause of Alzheimer’s disease—they suggested that Alzheimer’s may be an autoimmune disease.

Alzheimer’s May Be an Autoimmune Disease

According to statistics from the World Health Organization (WHO), there are about 50 million dementia patients in the world, with 10 million new cases every year; it means that about one person is diagnosed every three seconds.

Over the years, the “amyloid hypothesis” has been widely accepted among various theories of the cause of Alzheimer’s disease, but it has also been controversial as some phenomena in patients with Alzheimer’s do not fit the hypothesis. For example, people with amyloid plaques in their brains may not have Alzheimer’s. Besides, there are still many uncertainties about the clinical benefit of drugs targeting the elimination of amyloid beta.

Recently, Canadian scientists published a post saying that the amyloid beta found in the brains of Alzheimer’s patients is actually a substance released by the body’s immune response. They further speculate that Alzheimer’s is an autoimmune disease centered on the brain.

Autoimmune diseases refer to diseases caused by the body’s own immune system attacking the body. For instance, inflammations like arthritis and neuritis are autoimmune diseases.

The study looked at amyloid beta as a molecule normally found in the brain, that is, part of the brain’s immune system, rather than an abnormal protein.

Amyloid beta is a product of an integrated immune response that occurs in the brain when there is trauma or the presence of bacteria in it. The researchers also emphasized that stimulating events such as infection, trauma, ischemia, air pollution, and depression can trigger the body’s immune response, causing the secretion of amyloid beta.

Besides, in vitro experiments in the study showed that amyloid beta, as an antimicrobial peptide secreted by cells, also has immunomodulatory and antimicrobial properties.

However, when amyloid beta’s immunomodulatory and antibacterial properties mistakenly attack “self” neurons, it leads to changes in its membrane potential. The amyloid beta will enter neurons through the cell membrane and cause neuronal necrosis, which will trigger a series of chain reactions.

As neurons disintegrate after necrosis, the necrotic neuronal breakdown products diffuse to adjacent neurons, eliciting the further release of amyloid beta—everything keeps collapsing like dominoes and develops into a chronic self-perpetuating autoimmune cycle that eventually leads to Alzheimer’s disease.

The study also emphasizes that it is the necrotic neuronal breakdown products that elicit the release of amyloid beta and that the natural process of neuronal apoptosis does not significantly promote the release of this substance.

Other Evidence

In addition to having neurotoxic properties, amyloid beta was considered in this study as an antimicrobial peptide secreted by the human body. The researchers believe that when the human body is stimulated, it will mount an immune response and secrete amyloid beta to fight external challenges, as in vitro experiments have shown that amyloid beta also has antiviral and antibacterial functions, which also happen to be the basic properties of antimicrobial peptides secreted by the human body.

In experiments, amyloid beta was shown to be effective against the herpes simplex virus, as well as being able to kill and break down a variety of bacteria, including E. coli, S. aureus, S. marcescens, and K. pneumonia. The researchers believe that these experimental results support the view that Alzheimer’s is an autoimmune disease.

There are many potential causes of Alzheimer’s and its clinical manifestations are also very complex. However, there are other clues in related research that point to Alzheimer’s being an autoimmune disease.

A 1993 article in the Science journal suggested that Alzheimer’s may be caused by problems with the immune system, as a small trial showed that an anti-inflammatory drug could slow down Alzheimer’s disease.

A 2005 study reported abnormal levels of immunoglobulins in the brains of Alzheimer’s patients and, more importantly, antibodies from blood were also found in neuronal pathology and apoptosis.

According to the Alzheimer’s Association report, the risk of developing Alzheimer’s for a woman at age 65 is approximately 1 in 6, while the risk for a man is nearly 1 in 11 (i.e. women are 1.8 times more likely to develop Alzheimer’s than men), and the incidence of some immune diseases is different in different gender groups. In 2014, some researchers suggested based on this fact that Alzheimer’s is likely to be an autoimmune disease and proposed the idea of treating it with anti-inflammatory drugs.

In addition, a study confirmed that the blood-brain barrier in patients with Alzheimer’s is damaged, and the compromised blood-brain barrier may provide greater access for autoantibodies to invade brain tissues.

Tryptophan Metabolites May Serve as a Treatment for Alzheimer’s Disease

Researchers believe that if Alzheimer’s is indeed an autoimmune disease, it can be treated and intervened similarly to other autoimmune diseases by using endogenous immunomodulators.

It’s worth noting, however, that the study’s director, Donald Weaver, a professor of chemistry at the University of Toronto and director of the Krembil Research Institute, told The Epoch Times that “Alzheimer’s may be an autoimmune disease, but it does not mean that drugs (e.g. steroid based therapies) used to treat other autoimmune diseases (e.g. rheumatoid arthritis) will work against this disease. 

This is because the brain is different and will require specially designed and developed new drugs to target autoimmunity within the brain.”

Weaver further stated that the focus of his team’s work will be “to devise new therapeutics routes based on the novel theory that Alzheimer’s is an autoimmune disease” and that their goal is to “identify a chemical which normally occurs in the human brain and to use this as a starting point in the design of new drugs for Alzheimer’s.”

Studies have found that certain metabolites of tryptophan (amino acid) have anti-amyloid beta aggregation activity. Therefore, small-molecule analogs of tryptophan metabolites may be the development direction of new drugs for the treatment of Alzheimer’s as an immune disease.

In addition to Weaver and his team’s study, other clinical data in Alzheimer’s disease patients have also shown multiple associations with tryptophan metabolism. For example, with age, the human serum tryptophan level will decrease, and the plasma tryptophan level of Alzheimer’s patients will decrease; besides, acute depletion of tryptophan can lead to cognitive impairment.

So, can a tryptophan-rich diet prevent or treat Alzheimer’s disease?

Stephanie Zhang, a former research Scientist at The Memory Impairment and Neurodegenerative Dementia (MIND) Center at The University of Mississippi Medical Center, said in an interview with The Epoch Times that although this study focused on tryptophan metabolites, it cannot be directly deduced that a tryptophan-rich diet can affect Alzheimer’s disease.

However, some scientists have also proposed related treatment methods 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 diseases such as Alzheimer’s disease. 

Reposted from: https://www.theepochtimes.com/health/is-the-commonly-accepted-cause-of-alzheimers-wrong-expert-its-an-autoimmune-disease_4865585.html