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

Summary: Rather than simply being a brain disease, researchers propose that Alzheimer’s disease could be a disorder of the immune system within the brain.

Source: the conversation

The search for a cure for Alzheimer’s disease is becoming an increasingly competitive and controversial pursuit and recent years have witnessed several major controversies.

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

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

With millions of people in need of effective treatment, why are researchers still searching for a cure for what is arguably one of the most important diseases facing humanity?

Escape from the beta-amyloid rut

For years, scientists have focused on trying to find 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 gotten into a bit of an intellectual rut by focusing almost exclusively on this approach, often neglecting or even ignoring other possible explanations.

Unfortunately, this dedication to studying abnormal protein clusters has not translated into a useful drug or therapy. The need for a new “out-group” 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 devising a new theory of Alzheimer’s disease. Based on the last 30 years of research, we no longer think that Alzheimer’s is primarily a disease of the brain. Rather, we believe that Alzheimer’s is primarily a disorder of the immune system within the brain.

The immune system, found in every organ of 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 repair damaged tissue. When someone experiences a viral or bacterial infection, the immune system helps fight these microbial invaders.

The same processes are present in the brain. When there is trauma to the head, the brain’s immune system is activated to help repair it. When there are bacteria in the brain, the immune system is there to fight.

Alzheimer’s as an autoimmune disease

We believe that beta-amyloid is not an abnormally produced protein, but 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 key contributor to the brain’s comprehensive immune response. And this is where the problem begins.

Because of the striking similarities between the fat molecules that make up the membranes of both bacteria and brain cells, beta-amyloid cannot distinguish between invading bacteria and host brain cells, and mistakenly attacks the very brain cells they are supposed to be. protecting

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

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

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This shows a brain
Based on the last 30 years of research, we no longer think that Alzheimer’s is primarily a disease of the brain. The image is in the public domain

The brain is a very special and distinctive organ, recognized as the most complex structure in the universe. In our model of Alzheimer’s, 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.

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

Other theories of disease

In addition to this autoimmune theory of Alzheimer’s, many other new and varied theories are beginning to appear. For example, some scientists believe that Alzheimer’s is a disease of tiny cellular structures called mitochondria, the energy factories of each brain cell. Mitochondria convert the oxygen in the air we breathe and the glucose in the food we eat into the energy needed to remember and think.

Some argue that it is the end result of a particular brain infection, and bacteria in the mouth are often suggested to be the culprit. Others suggest that the disease may arise from abnormal handling of metals within the brain, possibly zinc, copper or iron.

It is gratifying to see new ideas about this age-old disease. Dementia currently affects more than 50 million people worldwide, with a new diagnosis every three seconds. People living with Alzheimer’s disease often cannot recognize their own children or even their spouse of over 50 years.

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

About this Alzheimer’s disease research news

Author: Donald Weaver
Source: the conversation
Contact: Donald Weaver – The Conversation
Image: The image is in the public domain

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