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Why has there been so little progress on Alzheimer's disease?

freakonomics.com

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Re: Why has there been so little progress on Alzheimer's disease?

#261

Post by rob_c »

jleyank wrote: post #30

They had a biological model. They had multiple drugs that were showed activity against that model, and effectiveness in humans. Problem was, the model was wrong. Pharma’s burned billions chasing this as it’s possibly the biggest market imaginable. Whether it was fraudulent or just incorrect is a different question. We don’t know all of the details of human biology. We don’t even know what all we don’t know. Most gues…

> Whether it was fraudulent or just incorrect is a different question.

Sorry but good science should be reproducible an given the amount of major retractions around this field I think this starts to become more than a passing question.

Lots of work is built on top of the model which means a lot of money change hands and a lot of honesty hard work was done.

Those who built the bad model should be being asked why a) they were so wrong (bad conclusions are fine) b) their data was so bad (this is not defensible) c) they didn't push for reproducing their work sooner to support the field (more of a daming statement of a field which treats a statistical analysis as a push button tool)...

Re: Why has there been so little progress on Alzheimer's disease?

#262

Post by Drupon »

DavidSJ wrote: post #197
Drupon wrote: post #108

Earlier quoted context omitted.

>I am David Schneider-Joseph, an engineer formerly with SpaceX and Google, now working in AI safety. Alzheimer’s isn’t my field If anyone wants to know who wrote the article linked before wasting time reading it, there you go.

Many in this thread, who have evidently spent very little time studying the topic, have confidently concluded the experts are wrong. I, also a non-expert, spent six months studying what the experts are doing, concluded that they actually seem to know what they’re talking about, and shared my understanding of that with other non-experts. If you’re going to dismiss me for saying the experts are right, since I’m not an…

>then shouldn’t you dismiss those who spent far less time than I to learn about the subject, who are saying the experts are wrong

Already have

Re: Why has there been so little progress on Alzheimer's disease?

#263

Post by rob_c »

raverbashing wrote: post #250
tim333 wrote: post #245

Earlier quoted context omitted.

Climate science is much more complicated - there are many things you could disagree with beyond will tons of carbon change things, yes or no. Like are we doomed or will it just get a bit warmer before we switch to solar for example. There are also money issues like with the alzheimer's situation. If climate change is dooming us then we should send more money to climate scientists.

> There are also money issues like with the alzheimer's situation. (that is: If climate change is dooming us then we should send more money to climate scientists) Absolutely, the issues are similar And if this can upend the business model of some big companies we'll give some "incentives" to some "doubtful" scientists even if their doubts are unfounded (actually very well founded but you get the gist) Which sucks bec…

> we should send more money to climate scientists.

Couldn't disagree more.

Please spend it on those who might actually fix something. There's plenty of can remove carbon or can undo the effect of X on Y. Let's stop falling back on the bad argument of we must leave nature alone right after arguing we change billion dollar industries because we can.

We shouldn't learn to be custodians watching the planet die because of past mistakes, we should be fixing and improving the planet and improving on nature because we can, must and should, shoulder this reaponsibility.

Please not _yet more modelling_ burning HPC into the ground just for a crappy bar line graph (based on assumptions)...

Re: Why has there been so little progress on Alzheimer's disease?

#264

Post by pcrh »

zosima wrote: post #252

The genetic evidence that amyloid-beta is in some way causative of at least a subset of Alzheimer's disease is still extremely strong. The fact that amyloid-beta binding drugs like Lecanemab and Donanemab decrease progression is also very strong evidence for the amyloid-beta hypothesis. What seemed to be the hurdle was likely, that targeting amyloid-beta in its pathological form just wasn't easy and developers of pha…

Unfortunately the evidence that targeting amyloid (e.g. Lecanemab and Donanemab) improves the symptoms of Alzheimer's disease is very weak. See the latest systematic review [0]. This does not mean however that amyloid plays no role in the disease, the treatment may simply be too late.

[0] https://www.cochrane.org/evidence/CD016297_are-medicines-ant...

Re: Why has there been so little progress on Alzheimer's disease?

#265

Post by anon84873628 »

nickburns wrote: post #69
anon84873628 wrote: post #61

Earlier quoted context omitted.

Gee, that sure is a confident statement of fact. Or maybe virus activity is one way that a negative feedback loop involving protein aggregates can begin ...

Sure is a line of inquiry worth pursuing either way, no?

It very much has been. Which is why it's tiring to see these articles (and HN comments) portraying it otherwise. Search HN for Alzheimer's and you will find lots of updates on the research and lots of the same uninformed comment threads.

Re: Why has there been so little progress on Alzheimer's disease?

#266

Post by zosima »

pcrh wrote: post #264
zosima wrote: post #252

The genetic evidence that amyloid-beta is in some way causative of at least a subset of Alzheimer's disease is still extremely strong. The fact that amyloid-beta binding drugs like Lecanemab and Donanemab decrease progression is also very strong evidence for the amyloid-beta hypothesis. What seemed to be the hurdle was likely, that targeting amyloid-beta in its pathological form just wasn't easy and developers of pha…

Unfortunately the evidence that targeting amyloid (e.g. Lecanemab and Donanemab) improves the symptoms of Alzheimer's disease is very weak. See the latest systematic review [0]. This does not mean however that amyloid plays no role in the disease, the treatment may simply be too late. [0] https://www.cochrane.org/evidence/CD016297_are-medicines-ant...

That systematic review is unfortunately severely flawed. They pooled the old anti-amyloid antibodies (which everybody agrees are inefficacious) and were never used outside clinical trials, with the new anti-amyloid antibodies, that does show modest efficacy in reducing the speed of progression.

While these two classes of drugs target the same molecule, they are developed to target amyloid-beta in very different forms. Pooling all those drugs together, and then showing very weak effect, makes absolutely zero sense, and I hope and expect this review to be pulled soon.

Re: Why has there been so little progress on Alzheimer's disease?

#267

Post by anon84873628 »

DANmode wrote: post #228
josh-wrale wrote: post #218

Earlier quoted context omitted.

Point stands.

So does the lack of a model for Alzheimer’s, and other chronic illnesses, that the consumer-facing medical industry prefers to dismiss.

The tau hypothesis is looking like a good model.

Re: Why has there been so little progress on Alzheimer's disease?

#269

Post by ori_b »

jvanderbot wrote: post #238
jhedwards wrote: post #193

Earlier quoted context omitted.

> It's much like climate science today: any dissent at all, even just questioning the predictions of catastrophe, immediately brands you as a heretic. I'm not sure I understand this. We've added hundreds of gigatons of carbon to the atmosphere. There's no mystery here, it's basic physics and chemistry that this will change things, and it's accepted that we don't know exactly _how_ things will change. The alternative:…

Yes I believe GP was focused on the catastrophe part. It's very likely correct that our CO2 emissions are warming the atmosphere ocean etc, but it's not clear that runaway warming is inevitable or that life or geology have feedback mechanisms that turn an exponential into an S curve. That is, after all, basically what natural selection tends to do. Turning the table again, even if there are corrective factors humans…

> but it's not clear

What better way to find out than to just try it and see if we end up with runaway warming? That surely can't cause any harm.

Re: Why has there been so little progress on Alzheimer's disease?

#270

Post by Aperocky »

mehrshad wrote: post #42

https://www.statnews.com/2019/06/25/alzheimers-cabal-thwarte... "Despite being described as a “cabal,” the amyloid camp was neither organized nor nefarious. Those who championed the amyloid hypothesis truly believed it, and thought that focusing money and attention on it rather than competing ideas was the surest way to an effective drug. It has not worked out that way. Research focused on amyloid, and the developmen…

They say science advance one death at a time.. let's hope LLM/AI can fix that by giving resource previously inaccessible to smaller players to be able to show results against the consensus.

Otherwise we just need to hope that we live long enough and don't catch ALZ until the current ruling peer group pass.

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