What if the presence of beta amyloid is not the cause of Alzheimer’s but rather the symptom? In that case, these drugs should be ineffective.
It would be interesting to see how brain function continues to be impaired even while the beta amyloids are suppressed using these drugs, helping us get to the real process.
Disclaimer: I am not a doctor, just try to follow up on big things impacting many people.
According to my understanding of the amyloid cascade hypothesis, the amyloid beta accumulation is not a cause but indeed a symptom (of gene mutations/something). Then, the amyloid beta basically clumps up and other mechanisms happen and neurons get damaged and this collective damage is known as Alzheimer's Disease.
So the amyloid beta is just one link in the chain.
Even with a complete removal of that link (removing/reducing amyloid beta), one cannot expect the disease to be reversed, since removal of something in-between does not revert the already occured damage. But accumulation of new damage might slow down. Coupled with improved early detection even this would be very helpful to many people.
As far as I know, some modest slowing down was observed in some of the clinical trials. This could mean the amyloid cascade hypothesis isn't completely wrong.
Now, what I found really, really interesting is that first Biogen gets ca. 20 % of its market value vaporized after the aducanumab (a joint venture betwen Biogen and Eisai). This is nearly 20 billion USD. Then, Eisai informs that they still go forward with another substance called BAN2401.
The BAN2401 also targets amyloid beta, but in a different way than others (protofibrils).
So... I'm thinking here that this is either a genius move or a really dumb one. It cannot really be anything in-between. I honestly hope it'll be a genius move.
Yes, obviously that is possible and now even likely. Given what was known at the time, it was reasonable to target amyloid. There are reams of papers studying beta amyloid and all the myriad downstream effects on neurophysiology, but it could turn out to just be an intermediary step.
It's the maddening thing about biology. It's a brutal intellectual undertaking. You could have spent your life studying amyloid. Imagine sitting in your office with your stacks of papers now, considering what you have done with your life.
For those willing (or those with power of attorney), would nanoparticle research experiments be worth the wont, per OP's point? While two major drug trials are being dropped towards the amyloid target (based on aducanumab) on public display, why not look towards AI and neuroplasticity measures to find the next set of targets
It would be interesting to see how brain function continues to be impaired even while the beta amyloids are suppressed using these drugs, helping us get to the real process.