| ▲ | gruez 11 hours ago |
| > Problem was, the model was wrong. I thought despite the fraud, it's still the best model we have[1]? The fact there was fraud doesn't mean the model is immediately incorrect. At best, it means its foundations are shakier than we thought, but it's not a slam dunk repudiation. [1] https://www.astralcodexten.com/p/in-defense-of-the-amyloid-h... |
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| ▲ | bradley13 3 hours ago | parent | next [-] |
| Pretty clearly not. It would seem that beta amyloids correlate with Alzheimer's, but do not cause it. The problem us "consensus science". You could get funding to research beta amyloids, but not to research any competing hypotheses. It's much like climate science today: any dissent at all, even just questioning the predictions of catastrophe, immediately brands you as a heretic. |
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| ▲ | stingraycharles 2 hours ago | parent | next [-] | | > 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 think this is not a great example, as there’s a huge group of people that, in fact, does not agree with the consensus and would happily fund research that (tries to) prove otherwise. I fully agree with your point, though, just not the example. | | |
| ▲ | hotstickyballs 2 hours ago | parent | next [-] | | That’s not true. If you want to have a job at a prestigious institution then the research committees are pretty consistent in their biases. | | |
| ▲ | acdha an hour ago | parent [-] | | Expecting scientific rigor is not a bad bias: everyone who has been willing to do actual science agrees that climate change is real and significant. For example, Richard Muller was a climate skeptic who had a great job at one of the most prestigious universities in the world, got funding to establish a team to critically review climate science research … and concluded it was right: “When we began our study, we felt that skeptics had raised legitimate issues, and we didn’t know what we’d find. Our results turned out to be close to those published by prior groups. We think that means that those groups had truly been very careful in their work, despite their inability to convince some skeptics of that.” https://www.nas.org/blogs/article/after_climate_research_phy... If you haven’t read up on both, it’s hard to appreciate how unlike climate science is from the beta amyloid theory. The latter has some evidence but there were always alternate theories by serious researchers because it involved multiple systems which scientists were still working to understand and basic questions around causation and correlation had significant debate. In contrast, climate scientists reached consensus about climate change four decades ago and by now have established many separate lines of evidence which all support what has been the consensus position. More importantly, since the 1970s they have been making predictions which were subsequently upheld by measured data from multiple sources. The ongoing research is in fine-tuning predictions, estimating efficacy of proposed interventions, etc. but nobody is seriously questioning the basic idea. Almost all of the people you hear dismissing climate change are funded by a handful of companies like Exxon, whose own internal research showing climate change was a significant threat produced a chart in 1982 which has proven accurate: https://skepticalscience.com/pics/Exxonpredictions.png https://insideclimatenews.org/news/16092015/exxons-own-resea... | | |
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| ▲ | defrost 2 hours ago | parent | prev [-] | | Over the past decades the group that are not happy with the AGW consensus in the hard earth sciences crowd have principally funded FUD via think tanks, ala the pro-tobacco lobby back in the day, rather than research. The few examples of research driven from the skeptic PoV (eg: urban heat skewing, etc) have landed on the side of the AGW consensus. |
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| ▲ | pas 2 hours ago | parent | prev | next [-] | | half the stuff currently in clinical trials is not targeting amyloids. https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/trc... | |
| ▲ | enraged_camel 3 hours ago | parent | prev [-] | | >> It's much like climate science today: any dissent at all, even just questioning the predictions of catastrophe, immediately brands you as a heretic. Nonsense. It is actually quite unlike climate science, where the consensus of catastrophe and the evidence for it are both overwhelming. Dissenters are listened to only to the extent they can provide overwhelming evidence to the contrary, which they so far cannot. |
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| ▲ | Drupon 6 hours ago | parent | prev | next [-] |
| >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. |
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| ▲ | fn-mote 2 hours ago | parent | next [-] | | For you, simply listing the author of the post is enough to discard it. Not everyone is that well informed, so it would be helpful for you to add another sentence explaining why this author has no credibility with you. | | |
| ▲ | jkman an hour ago | parent [-] | | It is self-evident? What do you mean. The guy is not an expert, end of story |
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| ▲ | trhway 6 hours ago | parent | prev [-] | | there is even easier way to estimate the chances of time wasting - it is a "rationalist" website, an "effective altruism"-like version of rationality. wrt. original post - quickly googled, and that for example https://www.news-medical.net/health/What-are-Amyloid-Plaques... - pretty short and seems to be clear that amyloids do have some correlation while may or may be not the cause. "Amyloid plaques form one of the two defining features of Alzheimer’s disease, the other being neurofibrillary tangles" Interesting that the latter is inside the neurons while the former is outside - speaking of complexity. The article also describes that activating microglia back helps with amyloid plaques while this https://pubmed.ncbi.nlm.nih.gov/33010092/#:~:text=The%20stud... "The neurofibrillary tangles (NFT) and amyloid-ß plaques (AP) that comprise Alzheimer's disease (AD) neuropathology are associated with neurodegeneration and microglial activation. " Human body reminds a large monolith codebase - fixing one thing breaks some other :). Claude Code, Human Body CRISPR edition, can't come soon enough... | | |
| ▲ | ifwinterco 5 hours ago | parent [-] | | Huge codebase with years of fixes, features and hacks added on top and nothing ever refactored. It’s a miracle it works at all | | |
| ▲ | generic92034 4 hours ago | parent | next [-] | | It is worse. The code changes are mostly random, only surviving the tests of fitness nature is applying (on various levels though; immediately catastrophic changes on level of cell biology are sorted out). And at least the high-level tests are also random and unreliable. | | |
| ▲ | ravenstine 3 hours ago | parent [-] | | So basically it's a codebase mostly composed of bugs, and the features mysteriously work because they're based on bugs that happen to be mitigated by other bugs. :) |
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| ▲ | 3 hours ago | parent | prev [-] | | [deleted] |
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| ▲ | mnode 7 hours ago | parent | prev | next [-] |
| Many in the research community realised the model was wrong a long time ago. This is a great read about the reasons why: 'How not to study a disease: the story of Alzheimer’s.' by Karl Herrup. |
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| ▲ | ACCount37 5 hours ago | parent [-] | | Wrong or incomplete? The current findings seem consistent with "both plaques and tangles are significant components of the pathology" and "our interventions are typically late and the accumulated neurological damage is already extreme by the time clinical symptoms show". Attacking the plaques wasn't completely worthless - findings show that this often slows disease progression, especially in early cases. There are pre-symptomatic trials ongoing that may clear the air on whether "intervention is late" is the main culprit in treatment underperformance. |
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| ▲ | friendzis 5 hours ago | parent | prev [-] |
| It's a classic example of "correlation does not imply causation". It was indeed observed that some patients with neurodegenerative conditions do indeed have amyloid plaques. It was further observed that patients with known Alzheimer's do not necessarily have amyloid plaques and patients without it do have plaques. The existence of amyloid plaques itself or the level, apparently, correlates extremely poorly, if at all, with the existence, onset or severity of the disease. Drugs attacking amyloid plaques might work, but they don't reverse the disease and do very little to slow progression. That's all scientific observations. > I thought despite the fraud, it's still the best model we have[1]? It is observed that one of the features of neurodegenerative diseases is decline in glucose metabolism. Supplementing energy availability (e.g. ketones [1], creatine [2]) does improve symptoms in patients with wide variety of CNS diseases, including Alzheimer's, senile dementia, epilepsy, and migraines. The ATN model you have linked might as well be just ONE OF possible pathways to glucose uptake inhibition, which could be the causal pathology of the symptoms. So no, it is very much not necessarily the best model we have. Inhibiting any pathway towards a disease is always a good thing, but the characteristics of "best" models are broad applicability and we have a serious contender. [1]: https://link.springer.com/article/10.1016/j.nurt.2008.05.004
[2]: https://alz-journals.onlinelibrary.wiley.com/doi/full/10.100... |
