Why Alzheimer’s may be an autoimmune disorder

For years, the conventional wisdom about Alzheimer’s disease was that it was a disease of the brain.

Research and treatments zeroed in on beta-amyloid proteins, substances that build up as plaques in the brain and are believed to trigger Alzheimer’s.

But recent studies are exploring other potential causes of Alzheimer’s. And some of them are indicating this devastating condition may not be what we think it is…

Alzheimer’s as an immune disorder

In 2022, a key research paper from 2006 that identified beta-amyloid as the cause of Alzheimer’s was exposed as having potentially been based on fabricated data.

Given that at least one treatment for Alzheimer’s, aducanumab, targets beta-amyloid, this could be an important revelation. Aducanumab has already been slated to be discontinued by its manufacturer.

Even before these events, some scientists have gone beyond the beta-amyloid hypothesis to investigate other potential mechanisms behind Alzheimer’s. In fact, one laboratory at the Krembil Brain Institute, part of the University Health Network in Toronto, has devised a theory that Alzheimer’s could be a disorder of the immune system within the brain.

In other words, they think Alzheimer’s is an autoimmune disease.

Beta-amyloid: the brain’s friend and foe

The immune system is found in every organ in the body and jumps into action to repair injuries and protect against foreign invaders.

This is true of the brain as well. When there is head trauma, the brain’s immune system is activated to help repair the damage. And when bacteria are present in the brain, the immune system fights them off.

What the Krembil scientists believe is that beta-amyloid is a normally occurring molecule that is part of the brain’s immune system, rather than an abnormally produced protein. When the brain needs to defend against injury or invaders, beta-amyloid is a key contributor to the brain’s immune response.

Unfortunately, there are similarities between the fat molecules making up both the membranes of bacteria and the membranes of brain cells. These similarities mean beta-amyloid can’t tell the difference between invading bacteria and host brain cells. Thus, beta-amyloid attacks the brain cells it’s supposed to be protecting.

This leads to a chronic, progressive loss of brain cell function, ultimately culminating in Alzheimer’s and/or dementia.

It’s a dilemma: beta-amyloid performs a central function in the brain’s immune system, but beta-amyloid is also causing the deterioration of brain cells.

Traditional autoimmune therapies not the answer

So what about traditional autoimmune therapies? Steroid-based therapies can be effective for many types of autoimmune diseases, such as rheumatoid arthritis. But the Krembil scientists say these therapies will not work against Alzheimer’s because the brain is such a complex organ.

Instead, they believe targeting other immune-regulating pathways in the brain will lead them to new and effective treatment approaches for Alzheimer’s.

This image of Alzheimer’s as an immune disorder dovetails with some studies that have linked the use of certain vaccines with a reduced risk of developing Alzheimer’s. While it’s not clear exactly how these vaccines lower Alzheimer’s risk, one theory is that it has something to do with their activation of the immune system.

This immune disorder theory isn’t the only one that has emerged from recent research. Some experts believe Alzheimer’s is a disease involving the dysfunction of mitochondria in the brain cells. Mitochondria are the tiny factories that convert oxygen and glucose into the energy these cells require for thinking and remembering. Mitochondrial dysfunction is emerging as one of the key hallmarks of the aging process.

Other theories are that Alzheimer’s results from a specific brain infection that could be caused by bacteria from the mouth, or that it occurs because of an abnormal handling of metals such as zinc, copper or iron within the brain.

Can fighting inflammation help?

Going back to the Krembil theory of Alzheimer’s as an autoimmune disease, the connection does seem strong. Especially when you consider that more than 80 percent of people with an autoimmune condition are women and about two-thirds of Alzheimer’s diagnoses are also women.

Chronic inflammation is the result of an overactive immune system and can exacerbate autoimmune disorders. So it makes sense that controlling inflammation could be a helpful step to support the brain’s immune system.

Researchers at Brigham and Women’s Hospital in Boston looked to vitamin D and omega-3s — nutrients with inflammation-fighting credibility — to test their protection against autoimmune disease.

Participants who took both supplements for 5 years reduced the occurrence of autoimmune disease by 25 to 30 percent compared with those who got placebos only.

Also promising is that previous research has provided some indication that targeting brain inflammation can slow the progression of Alzheimer’s.

Whether it can keep it from developing is yet to be seen, but there are benefits that go beyond brain protection that make it certainly worthwhile to avoid an overactive immune system and inflammation.

Sources:

Alzheimer’s May Not Actually Be a Brain Disease, Expert Reveals — Science Alert

Mitochondria research and neurodegenerative diseases: On the track to understanding the biological world of high complexity — Mitochondrion