The search for a cure for Alzheimer’s disease has become an increasingly competitive and contentious endeavor, and several important controversies have emerged in recent years.
And in July 2022, the journal Science reported that a major 2006 paper published in the prestigious Nature journal that identified a subtype of a brain protein called beta-amyloid as the cause of Alzheimer’s disease may have been based on fabricated data.
And a year earlier, in June 2021, the U.S. Food and Drug Administration approved aducanumab, an antibody-targeting beta-amyloid, for the treatment of Alzheimer’s disease, although evidence supporting its use has been incomplete and conflicting.
Some doctors believe that aducanumab should never have been approved, while others believe it should be given a chance.
If millions of people are in need of effective treatment, why are researchers still hesitant to find a cure for perhaps one of the most serious diseases facing humanity?
For years, scientists have been trying to find new treatments for Alzheimer’s by preventing the formation of harmful clumps in the brain due to this mysterious protein called beta-amyloid.
In fact, it can be said that scientists have become entangled in an intellectual mess, focusing almost exclusively on this approach, often ignoring other possible explanations.
Unfortunately, this commitment to the study of abnormal protein masses has not translated into a useful cure or treatment. The need for a new “out of the box” way of thinking about Alzheimer’s disease is a top priority in brain science.
The lab of the Krembil Brain Institute, part of the Toronto Health Universities Network, is developing a new theory of Alzheimer’s disease.
Based on research over the past 30 years, we no longer think of Alzheimer’s primarily as a brain disease. Instead, we think Alzheimer’s is essentially a disorder of the immune system in the brain. The immune system, present in every organ of the body, is a group of cells and molecules that work in concert to help repair injury and protect against foreign invaders.
When a person stumbles and falls, the immune system helps repair damaged tissue. And when someone has a viral or bacterial infection, the immune system helps fight those germs.
Exactly the same processes occur in the brain. With a head injury, the immune system of the brain begins to recover. And when bacteria are present in the brain, the immune system is ready to fight back.
Amyloid beta is not believed to be an abnormally produced protein, but is a naturally occurring molecule that is part of the brain’s immune system. He must be there.
And when brain injury occurs, or when bacteria are present in the brain, beta-amyloid is a major contributor to the overall immune response of the brain. And here the problem begins.
Because of the striking resemblance between the lipid molecules that make up bacterial membranes and brain cell membranes, amyloid-beta cannot distinguish between invading bacteria and host brain cells and mistakenly attacks brain cells that should provide protection.
This leads to a chronic and progressive loss of brain cell function, eventually leading to dementia, all because the body’s immune system cannot distinguish between bacteria and brain cells.
When Alzheimer’s disease is seen as a false attack by the brain’s immune system on the very organ it is supposed to protect, Alzheimer’s disease looks like an autoimmune disease.
There are many types of autoimmune diseases, such as rheumatoid arthritis, in which autoantibodies play an important role in disease progression and in which steroid-based therapy may be effective. But these treatments will not work against Alzheimer’s disease.
The brain is a very special and special organ known as the most complex structure in the universe. And in the Alzheimer’s disease model, amyloid beta 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 traditionally used to treat autoimmune diseases may not work against Alzheimer’s disease, we strongly believe that targeting other immune regulatory pathways in the brain will lead to new and effective treatments for this disease.
Other theories about the disease
In addition to the autoimmune theory of Alzheimer’s disease, many new and varied theories are emerging. For example, some scientists believe that Alzheimer’s disease affects delicate 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 energy for memory and thinking.
Some claim it is the end result of a certain infection in the brain, and bacteria in the mouth is often cited as the culprit. Still others suggest that the disease may arise from improper handling of metals in the brain, perhaps zinc, copper or iron.
More than 50 million people worldwide currently suffer from dementia, and a new diagnosis is made every three seconds.
For the well-being of individuals and families living with dementia, for the social and economic implications for an already overburdened health care system, and for addressing the ever-increasing costs and demands associated with dementia, we need to better understand Alzheimer’s disease and its consequences. causes, and what we can do to treat it and help the people and families living with it.
The report was prepared by Donald Weaver, professor of chemistry and director of the Krimpel Research Institute, University Health Network, University of Toronto.
Source: Science Alert