Alzheimer’s may not be primarily a brain disease. A new theory suggests it’s an autoimmune disease

Pursuing a cure for Alzheimer’s disease is becoming an increasingly competitive and controversial quest with the past few years witnessing several significant controversies.

In July 2022, the journal Science reported that a key 2006 research paper published in the prestigious journal Nature, which identified a subtype of brain protein called beta-amyloid as the cause of Alzheimer’s disease, may have been based on fabricated data.

A year earlier, in June 2021, the US Food and Drug Administration had approved aducanumab antibody– targeting beta-amyloid, as a treatment for Alzheimer’s disease, although data supporting its use were incomplete and conflicting. Some doctors believe that aducanumab should never have been approved, while others believe it should be given a chance.

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With millions of people in need of effective treatment, why are researchers still messing around in this quest for a cure for what can be proven one of the main diseases confront human?

Escape the beta-amyloid rut

Scientists have been working for years to come up with new treatments for Alzheimer’s by preventing the formation of brain-damaging clumps of this mysterious protein called beta-amyloid. In fact, we scientists have arguably gotten into some sort of intellectual rut by focusing almost exclusively on this approach, often neglecting or even ignoring other possible explanations.

Unfortunately, this dedication to studying the abnormal protein clumps has not translated into a useful drug or therapy. The need for a new “out-of-the-clump” way of thinking about Alzheimer’s is emerging as a top priority in brain science.

My lab at the Krembil Brain Institute, part of the University Health Network in Toronto, is developing a new theory about Alzheimer’s disease. Based on our research over the past 30 years, we no longer view Alzheimer’s as primarily a brain disease. Rather, we believe that Alzheimer’s disease is primarily a disease of the immune system within the brain.

The immune system, found in every organ in the body, is a collection of cells and molecules that work in harmony to help repair injuries and protect against foreign invaders. When a person trips and falls, the immune system helps to repair the damaged tissues. When a person experiences a viral or bacterial infection, the immune system helps fight these microbial invaders.

Exactly the same processes are present in the brain. When there’s a head trauma, the brain’s immune system kicks into gear to help recover. When bacteria are in the brain, the immune system is there to fight back.

Alzheimer’s as an autoimmune disease

We believe that beta-amyloid is not an abnormally produced protein, but rather a normally occurring molecule that is part of the brain’s immune system. It’s supposed to be there. When brain trauma occurs or when bacteria are present in the brain, beta-amyloid is a major contributor to the brain’s comprehensive immune response. And this is where the problem begins.

Alzheimer's Alzheimer’s disease is a public health crisis that needs innovative ideas and new avenues. (Source: Getty Images/Thinkstock)

Due to striking similarities between the fat molecules that make up both the membranes of bacteria and the membranes of brain cells, beta amyloid cannot tell the difference between invading bacteria and host brain cells, and mistakenly attacks the brain cells it is supposed to protect.

This leads to a chronic, progressive loss of brain cell function, eventually culminating in dementia – all because our body’s immune system can’t distinguish between bacteria and brain cells.

When considered a misdirected attack by the brain immune system on the organ it’s supposed to defend, Alzheimer’s emerges as an autoimmune disease. There are many types of autoimmune diseases, such as rheumatoid arthritis, where autoantibodies play a critical role in the development of the disease and for which steroid-based therapies can be effective. But these therapies will not work against Alzheimer’s disease.

The brain is a very special and distinctive organ, recognized as the most complex structure in the universe. In our model of Alzheimer’s disease, beta-amyloid helps protect and strengthen our immune system, but unfortunately it also plays a central role in the autoimmune process that we believe can lead to the development of Alzheimer’s disease.

While drugs conventionally used in the treatment of autoimmune diseases may not work against Alzheimer’s disease, we strongly believe that targeting other immune-regulatory pathways in the brain will lead us to new and effective treatment approaches for the sickness.

Other theories about the disease

In addition to this autoimmune theory of Alzheimer’s disease, many other new and varied theories are beginning to emerge. For example, some scientists believe that Alzheimer’s disease is a disease of small cellular structures called mitochondria — the energy factories in every brain cell. convert mitochondria oxygen from the air we breathe and glucose from the food we eat into the energy needed for remembering and thinking.

Some argue that it is the end result of a particular brain infection, with bacteria from the mouth often being suggested as the culprit. Still others suggest that the disease may arise from abnormal handling of metals in the brain, possibly zinc, copper or… iron.

It’s gratifying to see new thoughts on this age-old disease. Dementia currently affects more than 50 million people worldwide, with a new diagnosis every three seconds. Often people with Alzheimer’s disease are unable to recognize their own children or even their spouse over 50 years of age.

Alzheimer’s disease is a public health crisis that needs innovative ideas and new avenues. For the well-being of the people and families living with dementia, and for the socio-economic impact on our already stressed healthcare system, coping with the ever-increasing costs and demands of Dementiawe need a better understanding of Alzheimer’s disease, its causes, and what we can do to treat it and help the people and families living with it.

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