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.