[mjamesaustin]

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.

[lukeinator42]

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.

[anon84873628]

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.

[JamesBarney]

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.

[matthewdgreen]

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?

[celrod]

I think they're arguing

Cause -> cognitive disease Cause -> plaques

That is, that the same cause is behind both.

There may be some arrows from plaque to disease as well (i.e., that plaques also increase disease).

I dont know the truth, but just trying to understand/follow Alzheimers news and reading comments.

[pessimizer]

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.

[matthewdgreen]

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.