18 November 2023

Another Nail in the Amyloid Plaque Theory

When the brains of Alzheimer's patients are examined post mortem, there are large amounts of deposits on the nerves in the central nervous system known as amyloid plaques.

It has been dogma in the field for almost 50 years that this is the cause of this form of dementia, but it increasingly looks like these structures are not the cause of the condition, but rather a symptom, which has the effect of invalidating 50 years of basic and pharmaceutical research into the disease:

At the start of the 20th century, psychiatrist Alois Alzheimer became the first person to notice the strange clumps and tangles in the brain of a person who had died with dementia.

These bundles of amyloid beta proteins have since become the dominant hypothesis for what causes Alzheimer's disease. And, despite decades of failed studies, finding ways to clear them away has remained an obsession.

Now, in two trials, a drug designed to eradicate these sticky plaques has failed to preserve the cognitive abilities of people with early Alzheimer's disease compared to people given a placebo.

The monoclonal antibody gantenerumab did significantly reduce the amount of amyloid beta in the brain as intended, but this did not translate into improvements in cognitive function.

"Among persons with early Alzheimer's disease, the use of gantenerumab led to a lower amyloid plaque burden than placebo at 116 weeks but was not associated with slower clinical decline," the researchers reported in their paper covering the two drug trials.

These results arrive as the amyloid hypothesis reaches a critical juncture in its history – with pharmaceutical companies controversially winning anti-amyloid drug approvals based on thin evidence.

So, it is very likely we've been wrong for the past 50+ years. 

It's time to go to work and get a better understanding of the mechanisms involved.

It's time, to quote the movie The Martian, to, "Science the sh%$ out of this."



Post a Comment