This therapy doesn't target the amyloid-beta plaques. It repairs the blood brain barrier, and then the body is able to clear away the plaques. Their buildup is a symptom of Alzheimers, not the cause.
The problem with the amyloid-beta hypothesis was the assumption that these plaques were causing the Alzheimers and that removing them by itself could lead to a cure.
Exactly this. Amyloid-beta plaques and their association with dementia were discovered early on (late 1800s/early 1900s https://en.wikipedia.org/wiki/Amyloid_plaques#History), but the theory that they cause dementia hasn't panned out.
While the article emphasizes the BBB repair aspect, it seems the treatment does ultimately target plaques directly at a mechanical level:
>Normally, the protein LRP1 acts as a molecular gatekeeper, binding to Aβ and transporting it across the BBB for elimination. In Alzheimer’s, this system becomes fragile, leading to Aβ accumulation. The supramolecular drugs mimic LRP1 ligands, binding to Aβ and initiating its clearance, effectively resetting the system and restoring vascular function.
My sense of the narrative is that "unclogging" the amyloid protein with this treatment allows innate repair functions to resume.
I think amyloid being the proximate cause of neural degeneration in moderate and severe Alzheimers is basically disproven at this point.
I still think it's more likely than not (70%) that it is a cause though farther upstream. There is a good amount of evidence tau is more likely the proximate cause due it more closely tracking disability in moderate to late stage Alzheimer's.
Whoa there. Is that what’s happening? Cause an alternative theory is cause -> plaques -> cognitive disease. You seem to be arguing cause -> cognitive disease -> plaques, and I’m not sure this research demonstrates that. Does it?
Why does it seem like they're arguing that? I think that it's supposed to really be: cause -> (plaques = cognitive disease), and the fraud was (cause = plaques) -> cognitive disease.
As I took it, understanding that there was a fraud doesn't mean that continually clearing the plaques wouldn't have a good chance of holding off cognitive disease indefinitely.
I'm simply arguing that the plaques could be the proximate cause and the problem addressed by this treatment could be the remote cause. The OP is being vague in the way they stated it, but it feels like they're saying the plaques are irrelevant. That doesn't seem to fit what we know: the evidence that cognitive symptoms are downstream of plaques is pretty compelling.
I also don't think "fraud" should be used in this discussion at all.
With all that said, if this One Weird Trick can clear/prevent the buildup of plaques (and thus the cognitive symptoms downstream of them), that's just a best possible outcome.
Not saying it’s wrong or worthless, but do keep in mind that neither the author not the blog owner is in the medical field. That post is an outsider’s read of the consensus opinion from their investigation of the literature, including an estimate of the strength of that literature formed without expertise in the field itself.
It's correlated, much as body temperature is correlated with infection. But much like lowering body temperature won't cure the infection, directly addressing the amyloid-beta plaques doesn't seem likely to directly address Alzhimer's. Addressing the actual root cause may also make the plaques go away.
>"The long-term effect comes from restoring the brain’s vasculature. We think it works like a cascade: when toxic species such as amyloid-beta (Aβ) accumulate, disease progresses. But once the vasculature is able to function again, it starts clearing Aβ and other harmful molecules, allowing the whole system to recover its balance. What’s remarkable is that our nanoparticles act as a drug and seem to activate a feedback mechanism that brings this clearance pathway back to normal levels,”
>...
>Normally, the protein LRP1 acts as a molecular gatekeeper, binding to Aβ and transporting it across the BBB for elimination. In Alzheimer’s, this system becomes fragile, leading to Aβ accumulation. The supramolecular drugs mimic LRP1 ligands, binding to Aβ and initiating its clearance, effectively resetting the system and restoring vascular function.
So we may be lucky in that addressing the plaques as a symptom does indeed (allow for) repair of the underlying cause. I guess the question is how long the benefit lasts. What triggers the negative feedback loop in the first place? The article claims long term improvement for the mice, which were genetically programmed for amyloid production. (So maybe not an accurate simulation of the root cause, but perhaps actually more of a steel man test.)
It's very likely causative. There is just too much evidence for it not to be. All the genes related to amyloid processing are correlated with Alzheimer rates.
The most likely theory I've seen is amyloid causes tau buildup which leads to the majority of the damage. And by the time they give anti-amyloid drugs it's too late and the tau is doing the majority of the damage.
An analogy would be if you have a hole in your house which leads to getting a rat infestation. Once you notice the rat infestation patching the hole isn't going to solve your problem. The hole caused you to get rat shit on your counter, but by the time you fix the hole it's too late to stop the rats from shitting on your counter.
I thought amyloid-β buildup is usually determined at autopsy? That's not really the kind of diagnostic medicine I'm looking forward to. Can it also be determined via brain biopsy?
You can do PET imaging for it--there are a bunch of 18F-based tracers that work reasonably well. It also inversely correlates with Abeta levels in the CSF. Ne
Neither of those are particularly easy procedures, but certainly better than a biopsy (and autopsy!)
Fraudulent research should be treated as no-info, not a negative signal on the target. You can have fraudulent research supporting a correct theory. In fact this is more common, people will generally fake evidence to support a theory they think is probably true.
IIRC, it was revealed that treating this as a cause is wrong, it complicates or causes dementia, but is a symptom of something else, not a root cause of the disease.
But treating symptoms, esp restoring cognitive function, is a good thing.
This scandal comes to mind any time I see amyloid plaque research. Not sure if I misunderstood the scandal or if Alzheimer’s research has too much momentum to pivot. My dad was diagnosed a few years back and seeing stuff like this is always encouraging and infuriating because of this science article.
