The search for an Alzheimer's cure takes a different path

Oodles of money has been pumped into Alzheimer's Disease research over the years, and all we have to show for it is aducanumab, a controversial monoclonal antibody that targets amyloid plaques in the brain (approved on an accelerated schedule for use in the US, but not approved in Canada). The drug had inconsistent and contradictory clinical trial results, and faced significant debate over its effectiveness and widespread hesitation by doctors. Ultimately, it was withdrawn by its manufacturer, Biogen, when they realized they couldn't make any money from it.

Much of the difficulty in making any headway against Alzheimer's is because, thus far, the understanding that Alzheimer's is largely caused by clumps of a protein called beta-amyloid in the brain. This has been the conventional wisdom since the finding was published in a 2006 paper, and that is where almost all the effort towards a cure has been directed. Unfortunately, that paper was found to be based on fabricated data, and was retracted in 2024. Nearly 20 years wasted.

Since this retraction, research has opened up somewhat. Promising research right here in Toronto looks at beta-amyloid proteins not as a destructive abnormally-produced protein, but as part of the brain's immune system. The brain has its own immune system, just like the rest of the body and, when it encounters bacteria or trauma, it fights back, using beta-amyloid as a key contributor. Because the fat molecules making up the membranes of bacteria are very similar to the membranes of brain cells, the beya-amyloid can end up attacking the very brain cells it is supposed to be protecting, leading to chronic progressive loss of brain cell function, i.e. dementia.

This makes Alzheimer's (the most common type of dementia) not so much a disease of the brain as a disorder of the immune system within the brain, or an autoimmune disease. We do have steroid-based therapies against other autoimmune diseases like rheumatoid arthritis. But this kind of therapy will not work for the brain, but targeting other immune-regulating pathways in the brain may lead to new and effective treatments for the disease.

Either way, though, the search for a cure is pretty much back to square one.