The search for a cure for Alzheimer’s disease is becoming an increasingly competitive and contentious quest, with several significant controversies seen in recent years.
July 2022, Science magazine According to reports, the key 2006 research paper published in prestigious journal NatureThe study that identified a subtype of a brain protein called beta-amyloid as causing Alzheimer’s disease may have been based on fabricated data.
A year ago, in June 2021, U.S. Food and Drug Administration approves aducanumabThe drug, an antibody targeting beta-amyloid, was approved for the treatment of Alzheimer’s disease despite incomplete and conflicting data supporting its use.
Some doctors believe aducanumab should never have been approved in the first place, while others say it should be given a chance.
With millions of people in need of effective treatment, why are researchers still fumbling around in their search for a cure for one of the most significant diseases facing humanity?
Breaking out of the beta-amyloid rut
For years, scientists have been working to develop new treatments for Alzheimer’s disease. This mysterious protein prevents the formation of brain-damaging clumps It is called beta-amyloid.
In fact, it is fair to say that we as scientists have become intellectually bogged down by almost exclusively focusing on this approach and ignoring or dismissing other possible explanations.
Unfortunately, this effort to study abnormal protein clumps has not translated into useful drugs or treatments. The need for new ways to think “outside the clumps” about Alzheimer’s disease has emerged as a top priority in brain science.
In my lab at the Krembill Brain Institute, which is part of the University of Toronto Healthcare Network, A new theory of Alzheimer’s disease.
Based on research over the past 30 years, we no longer think of Alzheimer’s as a disease of the brain. Rather, it is primarily Impairment of the immune system in the brain.
The immune system is a collection of cells and molecules that are present in every organ in the body and work in harmony to help repair injury and defend against foreign invaders.
When a person trips and falls, the immune system helps repair damaged tissue. When a person contracts a viral or bacterial infection, the immune system helps fight off these microbial invaders.
The exact same process happens in your brain: if you have a head injury, your brain’s immune system jumps in to repair it. If there’s bacteria in your brain, your immune system fights back.
Alzheimer’s disease 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 there’s trauma to the brain or when there’s bacteria in the brain, beta-amyloid contributes significantly to the brain’s overall immune response, and that’s where the problems start.
Because of striking similarities between the fatty molecules that make up both bacterial and brain cell membranes, beta-amyloid is unable to distinguish between invading bacteria and host brain cells, and instead mistakenly attacks the very brain cells it is meant to protect.
This leads to a chronic, progressive loss of brain cell function and ultimately dementia, all because our body’s immune system cannot distinguish between bacteria and brain cells.
When Alzheimer’s disease is viewed as a condition in which the brain’s immune system mistakenly attacks the organs it is meant to protect, it emerges as an autoimmune disease.
There are many types of autoimmune diseases, such as rheumatoid arthritis, in which autoantibodies play a key role in disease development and which benefit from steroid-based treatments, but these treatments are ineffective for Alzheimer’s disease.
The brain is a very special and distinctive organ. The most complex structure in the universeIn our model of Alzheimer’s disease, beta-amyloid helps protect and strengthen the immune system, but unfortunately, it also plays a central role in the autoimmune processes that we think may lead to the development of Alzheimer’s disease.
Although drugs traditionally used to treat autoimmune diseases may not work for Alzheimer’s, we strongly believe that by targeting other immune regulatory pathways in the brain, new effective treatments for Alzheimer’s will be found.
Other theories about the disease
In addition to the autoimmune theory of Alzheimer’s disease, many other new and diverse theories are beginning to emerge. For example, some scientists believe: Alzheimer’s is a disease of tiny cellular structures called mitochondria – The energy factory in every brain cell.
Mitochondria convert the oxygen in the air we breathe and the glucose we take in from the food we eat into the energy we need for memory and thinking.
Some people think that Certain brain infectionsand It is often said that bacteria in the mouth is the cause.In addition, the disease Abnormal processing of metals in the brainProbably zinc, copper and iron.
I’m glad to see it A new way of thinking about this ancient diseaseDementia currently affects more than 50 million people worldwide, with a new diagnosis every three seconds. People with Alzheimer’s often cannot recognize their own children or even their spouses of more than 50 years.
Alzheimer’s is a public health crisis that requires innovative ideas and new directions.
For the well-being of people with dementia and their families, and because of the increasing costs and demands of dementia and the socio-economic impact on an already strained healthcare system, we need a better understanding of Alzheimer’s disease, its causes, and what can be done to treat it and help people with Alzheimer’s and their families.
Donald WeaverProfessor of Chemistry and Director of the Krembill Institute, University Health Network University of Toronto
This article is reprinted from conversation Published under a Creative Commons license. Original article.
A previous version of this article was published in September 2022.
