A Crisis in Alzheimer's Research

No, I haven't posted in a while.  For various reasons.  We are presently in Colorado to attend the wedding of our nephew to a wonderful young woman.  But something showed up on my news feed that was worth a comment.

According to the philosopher of science, Thomas Kuhn, a paradigm in a scientific theory ends when the evidence no longer supports the theory.  This is called a crisis for the theory.  So the theory of the solar system with earth at the center went into crisis when Copernicus showed evidence that the sun was the center.  From that crisis grew the heliocentric model (which is not as straightforward as believed in popular culture).  Well, some are saying that "the amyloid hypothesis" of Alzheimer's disease is now in crisis.

We discussed the amyloid hypothesis in Beating the Dementia Monster, noting that it's the most widely accepted hypothesis about how the disease begins and progresses.  Amyloid plaques build up on brain cells, interfering with the information passing between cells and killing the cells.  We also noted that this could be a complete misinterpretation of the data ... that amyloid plaques may actually be part of the body's effort to fight off bacterial or viral causes of the disease.

For sure, Aduhelm and Leqembi remove amyloid plaques and also produce some limited improvement in symptoms of the disease.  The assumption is that the disease slows because the plaques are being removed.  But now another monoclonal antibody successfully removes the plaques, but there has been little or no improvement in the condition of the patients.  This challenges the assumption that has underpinned the vast majority of Alzheimer's research and the pursuit of pharmaceutical treatments.

The monoclonal antibody is gantenerumab.  We did discuss this failure back in 2020, but the implications of this now seem to be sinking in.  Here's the article that caught my attention.

My early manuscript of Beating the Dementia Monster was actually quite skeptical of the amyloid hypothesis.  But reviewers led me to think I should tone that down, and so I did.  Maybe I should have kept my original treatment.