The search for a cure for Alzheimer’s disease is becoming an increasingly competitive and controversial quest, with recent years witnessing several significant controversies.
In July 2022, Science magazine reported that a key research paper from 2006, published in the prestigious journal Naturewhich identified a brain protein subtype 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 the antibody-targeting beta-amyloid aducanumab as a treatment for Alzheimer’s disease, even though the data supporting its use was incomplete and contradictory.
Some doctors think aducanumab should never have been approved, while others argue it should have a chance.
When millions of people need effective treatment, why are researchers still fumbling in the search for a cure for what is arguably one of the most significant diseases facing humanity?
Getting out of the amyloid beta rut
For years, scientists have focused on finding 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 ourselves into an intellectual rut by focusing almost exclusively on this approach, often neglecting or even ignoring other possible explanations.
Unfortunately, this dedication to the study of abnormal protein clumps has not translated into useful medicine or therapy. The need for a new way of thinking “outside the big picture” of Alzheimer’s disease 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 last 30 years of research, we no longer think of Alzheimer’s disease primarily as a disease of the brain. Rather, we believe that Alzheimer’s disease is primarily a disorder of the immune system in 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 stumbles and falls, the immune system helps repair damaged tissue. When a person experiences a viral or bacterial infection, the immune system helps fight off these microbial invaders.
The same processes are present in the brain. In head trauma, the brain’s immune system kicks in to help repair. When bacteria are present 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 molecule of normal origin that is part of the brain’s immune system. He’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 full immune response. And this is where the problem begins.
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 attacks by mistake. the very brain cells she’s supposed to be. protect.
This leads to a chronic and progressive loss of brain cell function, which eventually leads to dementia, all because our body’s immune system cannot tell the difference between bacteria and brain cells.
Viewed as a misdirected attack by the brain’s immune system against the very organ it is supposed to defend, Alzheimer’s disease appears to be an autoimmune disease.
There are many types of autoimmune diseases, such as rheumatoid arthritis, where autoantibodies play a crucial role in disease development and where steroid 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.
Although drugs traditionally 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 effective treatment approaches. for the disease.
Other disease theories
In addition to this autoimmune theory of Alzheimer’s disease, many other new and varied theories are beginning to appear. For example, some scientists believe that Alzheimer’s disease is a disease of tiny cellular structures called mitochondria – the energy factories of each brain cell.
Mitochondria convert oxygen from the air we breathe and glucose from the food we eat into energy for memory and thinking.
Some argue that it is the end result of a particular brain infection, with bacteria in the mouth often being suggested as the culprit. Still others suggest that the disease may result from abnormal handling of metals in the brain, possibly zinc, copper or iron.
It is gratifying to see new thinking about this age-old disease. Dementia currently affects more than 50 million people worldwide, with a new diagnosis being made every three seconds. Often, people with Alzheimer’s disease are unable to recognize their own children or even their spouse over the age of 50.
Alzheimer’s disease is a public health crisis that needs innovative ideas and new directions.
For the well-being of individuals and families with dementia, and for the socio-economic impact on our healthcare system already stressed by the ever-increasing costs and demands of dementia, we need a better understanding Alzheimer’s disease, its causes, and what we can do to treat it and help the individuals and families who suffer from it.
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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