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Comment by DarkmSparks | Hacker News Reader

last I heard everything amyloid/plaque burden was suspect after

https://www.nytimes.com/2023/07/19/us/stanford-president-res...

It looks very much like they are a symptom rather than a cause. They have got very good at medicines that remove amyloid/plaques, they only physical outcome was massive brain bleeds and death, plus a little

https://www.ncbi.nlm.nih.gov/search/research-news/13804/

before being withdrawn for all the reasons they resigned

https://www.pharmaceutical-technology.com/analyst-comment/bi...

absolute disaster :(

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Tau and it's relationship to Amyloid, are the current top hypothesis.

Another way to look at why the removal of amyloid may not be effective in repairing damage is to think of it like a blocked pipe.

A pipe gets blocked, and the pipe itself gets damaged, causing a leak. The block can be removed, but that doesn't repair the pipe.

In my example, the pharmaceuticals are removing the blockage, but the damage is still done.

Having said that, I believe that as we learn more about what we currently call Alzheimer's, we'll discover that we've been lumping multiple diseases under a single label. I believe the amyloid hypothesis, and Type 3 diabetes hypothesis, both have merit. There may well be others.

Traumatic brain injury (TBI) can lead to the rapid formation of amyloid plaques....

So entirely possible they are simply part of how or brain deals with brain cell death.

Its possible at this point it's not a "disease" at all, at least no more than the STI we are all dieing from (our parents had sex and now we get to die).

Prior to 1900 or so, average life expectancy was something like 25 or 30, our brains simply never evolved to live as long as they do now, some people age faster than others..

The problem for the scientific basis is all the brain research has gone into plaques and ignored all the other conditions that lead to cell death and aging, it's going to be a while before other directions can be properly explored, and plaques for sure still have the momentum despite failing at every turn.

Plaques have not failed at every turn. This seems to be a myth repeated every time an article like this pops up. Yes there were specific instances of fraud, but this did not invalidate the whole research avenue. Researchers are in fact doing exactly what you suggest, and understanding plaques is a lever into those underlying dysfunctions... Like say circadian rhythm perhaps.

And I don't know why you would talk about average life expectancy when median expectancy or expectancy at adolescence are much more relevant metrics (that probably don't agree with your point).

Name a single success.

The best treatments on the market slows cognative decline measurements for up to 6 months "maybe" (could just be the result of pain relief), dates back to like 2001, and have nothing to do with amyloids.

>but this did not invalidate the whole research avenue

Indeed, multiple treatments in very expensive human trials based on the research avenue failing to show any kind of measurable clinical efficacy invalidates the research area.

The latest being from just a few days ago

https://www.biospace.com/drug-development/alector-scraps-dem...

You're confusing repairing the damage with the cause.

Just because amyloid/tau cause the damage, that doesn't mean removing them repairs.

If rust weakens a structural piece of steel, removing the rust does not repair the integrity of the steel.

There is exactly zero evidence to show they cause the damage, the only evidence that once existed to say they caused the damage used 100% faked results, which didnt emerge until after the treatments based on it causing the damage failed to show any clinical benefit and stanford launched an investigation into the prof whose students produced the evidence.

They created several treatments that stopped them forming (most prominent being biogens). The result was no difference in cognitive function vs placebo and some 20% of the people who took it suffering from a heamoralgic stroke (which they covered up).

sources please!?

there's a reason that 18% of clinical trials around drugs against Alzheimer's still target plaques

also the etiological model evolved a lot (as others pointed out, it's removing blockage after the pipe has ruptured still can lead to a sinkhole forming later)

https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/trc...

also some nuance regarding the scientific fraud and the Amyloid mafia https://www.science.org/content/blog-post/reaction-alzheimer...

There are no sources, that is the definition of zero evidence.

Also, The fraud was found because the theory was invalidated, not the other way around. It was found that real life did not match the theory (by spending billions on human trials that all failed), so they looked back at the theory and found the results were fake.

There is however evidence that it doesnt. E.g. https://jamanetwork.com/journals/jamaneurology/fullarticle/1...

But it was and continues to be ignored.

When you say "the only evidence that once existed to say they caused the damage used 100% faked results", that is the kind of claim for which there could be evidence. What's more, it's the kind of claim that you should present evidence for when making the claim, since it's an attack on the credibility and honesty of those doing the study.

Sure, I am referring there to what started with

https://www.science.org/content/article/potential-fabricatio...

And finished with the resignation of the stanford prof engaged in it, and all the evidence that they cause cognitive imparment being retracted.

E.g.

https://www.nature.com/articles/nature04533

There is success every time we understand a new detail about how/why plaques form, how to detect them, and how to remove them. The science is pointing to a world where treating people much earlier in life (before cognitive symptoms actually appear, before tau forms) is going to prevent disease progression for the majority of people and effectively prevent Alzheimer's.

Not really true. See for instance this link

"Opponents call the amyloid hypothesis zombie science, propped up only by pharmaceutical companies hoping to sell off a few more anti-amyloid me-too drugs before it collapses. Meanwhile, mainstream scientists . . . continue to believe it without really offering any public defense. Scott was so surprised by the size of the gap between official and unofficial opinion that he asked if someone from the orthodox camp would speak out in its favor."

https://www.astralcodexten.com/p/in-defense-of-the-amyloid-h...

From that link

"and only slow progression a relatively small amount."

They don't even do that. they _do_ remove plaques, they _do not_ have any statistically significant effect on MMSE degradation.

plus I only see the comments that point out the entire scientific basis for them was based on faked research.

The way I had it "simply" described was "the plaques are basically dead brain cells, the problem is the brain cells rapidly dieing, not cleaning up the corpses afterwards".

either way, the faked research set dementia research back at least 2 decades and wasted billions of dollars on failed medications with no benefits and horrific side effects (that they tried to cover up).

Yep; this has frustrated me for two decades.

Dale Bredsen says the fundamental nature of Alzheimer's is a network insufficiency.

[redacted] in https://x.com/MetabolicFactor/status/1918558438440739258

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