Finding a cure for Alzheimer ‘s disease is becoming an increasingly competitive and contentious challenge, and several major controversies have occurred in recent years.
Finding a cure for Alzheimer’s disease is becoming an increasingly competitive and contentious challenge, and several major controversies have occurred in recent years.
Without going any further, in July 2022, the journal Science reported that a key research paper from 2006 identifying 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 an antibody targeting beta-amyloid called aducanumab as a treatment for Alzheimer’s, despite incomplete data supporting its use and contradictory.
If there are millions of people in need of effective treatment, how come researchers keep floundering? Why have they not yet found a cure for what is possibly one of the most important diseases facing humanity?
Escape the beta-amyloid rut
For years, treatments for Alzheimer’s have focused on preventing the formation of clumps of that mysterious brain-damaging protein called beta-amyloid. In fact, it could be said that we scientists have gotten into a bit of an intellectual rut by concentrating 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 way of thinking about Alzheimer’s “outside the clusters” is becoming 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 our last 30 years of research, we don’t think of it as a neural disease. Rather, we believe that Alzheimer’s is primarily a disorder of the immune system within the brain .
The immune system, found in every organ in the body, is made up 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 tissues. When someone experiences a viral or bacterial infection, the immune system helps fight these microbial invaders.
Well, in the brain the processes are exactly the same. When there is a head injury, the brain’s immune system kicks in to help repair. And if there are invading bacteria, the immune system is there to fight them off.
Alzheimer’s as an autoimmune disease
We believe that beta-amyloid is not an abnormal protein, but rather a normally generated molecule that is part of the brain’s immune system. When brain trauma occurs or when there are bacteria in the brain, beta-amyloid would be a key element in the brain’s overall immune response. And this is where the problem starts.
Due to striking similarities between the fat molecules that make up bacterial membranes and brain cell membranes, beta-amyloid cannot distinguish between invading bacteria and host brain cells. So it mistakenly attacks the very brain cells it’s supposed to be protecting.
This leads to a chronic and progressive loss of brain cell function, ultimately culminating in dementia.
If the source of the problem is a misdirected attack by the brain’s immune system against the very organ it is supposed to defend, then Alzheimer’s disease can be considered autoimmune.
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 will not work against Alzheimer’s disease. After all, the brain is a very special organ, recognized as the most complex structure in the universe .
However, even if the drugs conventionally used to treat autoimmune diseases fail in the brain, we strongly believe that working with other pathways of immune regulation in the thinking organ will lead to new and effective treatment approaches against the disease.
Other theories of the disease
In addition to this autoimmune theory of Alzheimer’s, many other approaches are beginning to appear. For example, some scientists argue that Alzheimer’s is a disease of tiny cellular structures called mitochondria , the powerhouses of cells. Mitochondria convert oxygen from the air we breathe and glucose from the food we eat into the energy needed to remember and think.
Others maintain that it is the end result of a particular brain infection , with bacteria from the mouth as the main suspect . There are also those that suggest that the origin is in an abnormal manipulation of metals in the brain , possibly zinc, copper or iron.
In any case, Alzheimer’s is a public health crisis that needs innovative ideas and new directions. It is gratifying to see new insights into this ancient disease . Let us not forget that dementia currently affects more than 50 million people worldwide, with a new diagnosis every three seconds.
For the well-being of individuals and families living with dementia, and for the socio-economic impact on our already stressed healthcare system coping 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 individuals and families who live with it.