Alzheimer’s may not really be a brain disease, says expert: ScienceAlert

The pursuit of a cure for Alzheimer’s disease is becoming an increasingly competitive and controversial quest that has witnessed several significant controversies in recent years.

In July 2022, Science magazine reported that a key research article from 2006, published in the prestigious journal Naturewhich identified a subtype of brain protein called beta-amyloid as the cause of Alzheimer’s disease may be based on fabricated data.

A year earlier, in June 2021, the U.S. Food and Drug Administration had approved aducanumab, an 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.

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

Escape the beta-amyloid rut

For years, scientists have been trying to devise new treatments for Alzheimer’s disease 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 disorder of the immune system in the brain.

Found in every organ in the body, the immune system 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.

Because of 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, which eventually leads to dementia – all because our body’s immune system cannot distinguish between bacteria and brain cells.

When viewed as a misdirected attack by the brain’s 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 to 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 disease.

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.

Mitochondria convert 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 people and families living with dementia, and for the socio-economic impact on our already strained health care system as it faces the increasing costs and demands of dementia, we need a better understanding of the Alzheimer’s disease, its causes, and what we can do to treat it and help the people and families living with it.The conversation

Donald WeaverProfessor of Chemistry and Director of the Krembil Research Institute, University Health Network, University of Toronto

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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