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AI helps unravel a cause of Alzheimer’s and identify a therapeutic candidate
- pedalpete 1y agoIts good to see them classifying this as for "late onset Alzheimer's". There is a theory that Alzheimer's as we currently understand it, is not one disease, but multiple diseases that are lumped into one category because we don't have an adequate test. This is also where some of the controversy surrounding the Amyloid hypothesis comes from.
- jvans 1y agoThe controversy over the amyloid hypothesis comes from a Stanford professor faking data[1] and setting the field back decades. The amount of harm this individual caused is hard to overstate. He is also still employed by Stanford. [1] https://stanforddaily.com/2023/07/19/stanford-president-resigns-over-manipulated-research-will-retract-at-least-3-papers/ https://stanforddaily.com/2023/07/19/stanford-president-resi...
- matthewdgreen 1y agoI know that it is very important for HN folks to be angry. But as someone who has a parent with this disease, I would like to be certain that the amyloid hypothesis is definitely not correct before we throw it entirely out with the bathwater. These simplified “one researcher caused an entire field to go astray for decades” explanations are much too pat for me to have any confidence in them.
- jvans 1y agoA lot of people should be mad at Marc Tessier-Lavigne, not just HN folks. He lied for personal gain at the expense of scientific progress and millions of patients who suffer
- dev1ycan 1y agoResearchers spent decades already on it and couldn't get results for a reason.
- DaiPlusPlus 1y ago> These simplified “one researcher caused an entire field to go astray for decades” explanations are much too pat for me to have any confidence in them. Right, monocausal explanations in-general will set-off my skept-o-sense too; but then my mind made me think of another example: Andrew Wakefield (except that AW succeeded more at convincing Facebook-moms than the scientific establishment - but still harmed society just as much, IMO)
- razakel 1y agoWakefield's fraud was quite sophisticated and did manage to fool many medical professionals.
- pedalpete 1y agoMy uncle died of the disease, and I work in neurotech/sleeptech, specifically in slow-wave enhancement which is showing promise in Alzheimer's. I 100% agree with you that we shouldn't throw the baby out with the bathwater on this one. Data being falsified and the hypothesis being wrong are two different things.
- apwell23 1y agois anyone pursuing the hypothesis then?
- literalAardvark 1y agoCan you recommend a reliable source for sleep improvement? The internet is awash in random garbage and it'd be interesting to have a link that someone who actually sees sleep EEGs thinks is "80% there". Re: Link, just to lower your load in answering.
- adastra22 1y agoThe amyloid hypothesis is absolutely not correct. We know this unequivocally. Amyloid deposits correlate with Alzheimer’s, but they do not cause the symptoms. We know this because we have drugs which (in some patients, not approved for general use) completely clear out amyloids, but have no affect on symptoms or outcomes. We have other very promising medications that do nothing to amyloids. We also have tons of people who have had brain autopsies for other reasons and found to have very high levels of amyloid deposits, but no symptoms of dementia prior to death. Alzheimer’s isn’t caused by amyloids.
- polskibus 1y agoI’m interested in this and it seems you have done your homework. Would you mind sharing some references?
- Aurornis 1y ago> These simplified “one researcher caused an entire field to go astray for decades” explanations are much too pat for me to have any confidence in them. Anyone who believes that an entire field and decades of researched pivoted entirely around one researcher falsifying data is oversimplifying. The situation was not good, but it’s silly to act like it all came down to this one person and that there wasn’t anything else the industry was using as their basis for allocating research bets.
- deleted 1y ago[deleted]
- bawolff 1y agoRegardless, it is still important not to fall into the fallacy fallacy (just because someone made a bad argument for something does not imply that the conclusion is neccesarily false)
- jcranmer 1y agoIt's actually pretty easy to overstate the amount of harm caused by that one individual... you're doing it. There are lots of good reasons to believe in the amyloid hypothesis, and no paper or even line of research is the one bedrock of the hypothesis. It was the foundational bedrock of Alzheimer's research back in the early 1990s (essentially, before Alzheimer's became one of the holy grail quests of modern medicine), after all; well before any of the fraudulent research into Alzheimer's was done. The main good reason not to believe in amyloid is that every drug targeting amyloid plaques has failed to even slow Alzheimer's, even when they do impressive jobs in clearing out plaques--and that is a hell of a good reason to doubt the hypothesis. But no one is going to discover that failure until you have amyloid blockers read out their phase III clinical trial results, and that doesn't really happen until about a decade ago.
- DavidSJ 1y agoevery drug targeting amyloid plaques has failed to even slow Alzheimer's Lecanemab and donanemab succeeded in slowing Alzheimer’s. As did gantenerumab in a recent prevention trial: https://www.alzforum.org/news/research-news/plaque-removal-delays-onset-familial-alzheimers-disease https://www.alzforum.org/news/research-news/plaque-removal-d...
- SwtCyber 1y agoThe more we learn, the more it feels like "Alzheimer's" is just a convenient label for a bunch of different underlying pathologies that happen to look similar on the surface.
- mobilejdral 1y agoTying this to APOE, specifically e4 which has an increased requirement for choline and when choline levels are low there can be a metabolic push that leads to elevated PHGDH activity and consequently, increased serine synthesis. That is a neat connection and maybe why when we study choline supplements we see positive results. https://www.sciencedirect.com/science/article/pii/S0002916524008694 https://www.sciencedirect.com/science/article/pii/S000291652...
- pedalpete 1y agoThat is super interesting, as is the relationship between choline and sleep. With restorative sleep function, and specifically slow-wave activity, considered to be a significant driver of AD. https://www.jarlife.net/3844-choline-sleep-disturbances-and-alzheimers-disease.html https://www.jarlife.net/3844-choline-sleep-disturbances-and-...
- mobilejdral 1y agoAnd then this ties to estrogen, HRT is known to reduce the risk of dementia/AD (https://pmc.ncbi.nlm.nih.gov/articles/PMC10480684/ https://pmc.ncbi.nlm.nih.gov/articles/PMC10480684/). PEMT (phosphatidylethanolamine N-methyltransferase) is what makes choline in the body, but it depends on estrogen.(https://pmc.ncbi.nlm.nih.gov/articles/PMC3020773/ https://pmc.ncbi.nlm.nih.gov/articles/PMC3020773/)
- pedalpete 1y agoYeah, part of my work is in dementia with slow-wave sleep enhancement, and we're putting together a menopause study hopefully to start in 2026.
- j45 1y agowow, thanks for sharing.
- xlbuttplug2 1y ago> In conclusion, our findings suggest that moderate dietary choline intake, ranging from 332.89 mg/d to 353.93 mg/d, is associated with lower odds of dementia and better cognitive performance. Gemini tells me that amounts to ~850mg of alpha GPC or ~1900mg of citicoline. Eggs it is then.
- rad_gruchalski 1y agoThis is an interesting observation: > With AI, they could visualize the three-dimensional structure of the PHGDH protein. Within that structure, they discovered that the protein has a substructure that is very similar to a known DNA-binding domain in a class of known transcription factors. The similarity is solely in the structure and not in the protein sequence.> Reminds me of: if you come across a dataset you have no idea of what it is representing, graph it.
- kylehotchkiss 1y agoPardon my poor bio education but couldn’t this same outcome have been reached if the protein was xray crystallographyed?
- falcor84 1y agoAre you arguing that an in-silico result could have alternatively been achieved in-vitro? Yes, I suppose it could, but it sounds like that joke "A month in the laboratory can often save an hour in the library".
- colingauvin 1y agoI worked for a while on extremeophile Archaeal viruses - the type that infect organisms that manage to live in volcanic hot springs, for instance. These are ecological niches that are old, and extremely divergent. There's little genetic exchange between life around the hot springs, and life within them. The typical route of discovering those viruses was first genetic. When you get a genome (especially back when this work was initiated), you'd BLAST all the gene sequences against all known organisms to look for homologs. That's how you'd annotate what the gene does. Much more often than not, you'd get back zero results - these genes had absolutely no sequence similarity to anything else known. My PI would go through and clone every gene of the virus into bacteria to express the protein. If the protein was soluble, we'd crystallize it. And basically every time, once the structure was solved, if you did a 3D search (using Dali Server or PDBe Fold), there would be a number of near identical hits. In other words, these genes had diverged entirely at the sequence level, but without changing anything at the structural (and thus functional) level. Presumably, if AlphaFold is finding the relationship, there's some information preserved at the sequence level - but that could potentially be indirect, such as co-evolution. Either way, it's finding things no human-guided algorithm has been able to find.
- bawana 1y agoI wonder if they used the output of alpha fold? Remember that Deepmind published the 3D structure of hundreds of millions of proteins for FREE. Imagine if they walled off that data behind an Elsevier like subscription wall? They shoould credit Deep Mind at least
- falcor84 1y agoGood point, the article [0] does mention AlphaFold but doesn't cite it. [0] https://www.cell.com/cell/fulltext/S0092-8674(25)00397-6 https://www.cell.com/cell/fulltext/S0092-8674(25)00397-6
- colingauvin 1y agoAlphaFold is regurgitating structural information from 10s of thousands of experimental structures acquired at great cost and published to the PDB for free, with no license restrictions of any kind.
- derektank 1y agoYou make a fair point but much of that work was funded by public grants, while AlphaFold was privately funded. Those generally come with different expectations
- HarHarVeryFunny 1y ago> With AI, they could visualize the three-dimensional structure of the PHGDH protein. Sure sounds like it.
- DaiPlusPlus 1y agoWhile I (loosely) understand the concept of using a custom (foundational?) machine-learning model to explore some problem-space and devise solutions, I don't understand why it says they used "AI" to "visualize" a structure. A layperson is going to think they simply asked ChatGPT to solve the problem for them and it just worked and now OpenAI owns the cure for Alzheimer's. ...I ask because bio/chem visualization and simulation was a solved problem back in the 1980s (...back when bad TV shows used renders of spinning organic-chemistry hexagons on the protagonist's computer as a visual-metaphore for doing science!).
- bitwize 1y agoI'm an AI skeptic but this is AI doing its job. Because there's AI as in "letting ChatGPT do the hard bits of programming or writing for me", for which it is woefully unsuited, and there's AI as in using machine learning as a statistical approach, which it fundamentally is. It's something you can pour data into and let the machine find how the data clump together, so you can investigate potential causative relationships the Mark I eyeball might have missed. I'm excited for the possibilities these uses of AI might bring.
- brailsafe 1y agoAgreed. I have barely any enthusiasm in the former aside from potential time savings, but have always been fascinated in the applications of what I think of as scientific deep large scale pattern matching in domains that aren't practical to tackle with raw human labor.
- insin 1y agoIt's a pity the ridiculous level of LLM overhype from those chasing investment and profit is dragging "AI" through the mud with it
- 01100011 1y agoThe ridiculous hype behind LLMs, like 3D gaming before it, is helping to pay for the advances in HW that enable this "AI".
- devmor 1y agoHell yes! This is where machine learning shines and I’m so happy to see another incredible breakthrough from using it in medical science. It’s a nice reprieve from “we’re using a chatbot as a therapist and it started telling people to kill themselves” type news.
- forrestthewoods 1y agoThis article is trashy trash trash. The only mention of AI in the actual paper is that they used ChatGPT for grammar correction. The article doesn't explain what or how AI was used beyond "three dimensional modeling". A paper author did quote the use of AI. But without explaining precisely how AI was used and why it was valuable this article is basically clickbait trash. Was AI necessary for their key result? If so how and why? We don't know! Everything about this screams "just say AI and we'll get more attention".
- AIPedant 1y agoThat's not true, the paper used AlphaFold 3. The disclaimer is about generative AI, not AI writ large. I agree the UCSD writeup is pretty misleading; the authors used protein-modeling software, which is really not very interesting, and the fact that the SOTA protein modeler uses machine learning is not at all relevant to this specific paper.
- forrestthewoods 1y ago> That's not true, the paper used AlphaFold 3 Ah yeah I skimmed and searched for “AI” so missed that. The UCSD article does not contain the term “AlphaFold” so yeah they’re definitely engagement baiting.
- jedberg 1y agoThis is a strong argument for universal healthcare. If we had universal healthcare in the USA, we'd have to have a common charting protocol and a medical chart exchange. One thing that AI/ML is really good at is taking very large datasets and finding correlations that you wouldn't otherwise. If everyone's medical chart were in one place, you could find things like "four years before presenting symptoms of pancreatic cancer, patients complain of increased nosebleeds", or things like that. Of course we don't need universal healthcare to have a chart exchange, and the privacy issues are certainly something that needs consideration. But the point is, I suspect we could find cures and leading indicators for a lot of diseases if everyone's medical records were available for analysis.
- smallnix 1y agoUniversal healthcare and having everyones medial chart stored centrally can be related, but must not be. There are many countries with some form of universal healthcare and no centralized records.
- jedberg 1y ago> There are many countries with some form of universal healthcare and no centralized records. I believe you, but I'm curious how that works. When you go to a random doctor, do they have to request your records from all your other doctors? Similar to here in the USA when you have a PPO?
- piotrkaminski 1y agoThat certainly used to be the case in Canada 20 years ago, don't know if they've standardized since.
- adastra22 1y agoYes. What’s surprising about this? The two topics seem orthogonal. Universal healthcare is about who is paying, not necessarily about who is running the service.
- ganterich 1y agoMinor nitpick about the headline. AI didn't help, it was used to identify a therapeutic candidate. I dislike personification of AI because people treat it as something religious already. AI doesn't do anything, the people using it do.
- mgraczyk 1y ago"seatbelts help people survive car accidents" This is a completely normal way to talk about inanimate objects
- derektank 1y agoI share your concern with anthropomorphizing AI tools but I don't think this is really a serious example. It seems fairly common to say a tool, even a rudimentary one, helps it's user in English. Spears helped hunter gatherers out compete other apex predators, road networks helped Rome maintain a large empire, solar panels help us reduce carbon emissions, etc.
- ganterich 1y agoI aggree with your point and the first comment about seatbelts, thanks for that perspective. The reason I personally still see an issue is that personification of AI is an actual issue, while personification of seatbelts and spears is not. This lands on the frontpage of hackernews, and people don't read every article on the frontpage, but they read the headlines, and the headlines carry latent messages that get interpreted. And with the huge hype around LLMs, AI for most people means LLMs. So most people will read this headline and not the article and subconsciously concluce that researchers used LLMs to solve Alzheimers, further strengthening their religious belief LLMs were mystical oracles of truth, potentially able to solve widespread deadly diseases, while not realizing that the researchers might have used highly specialized machine learning or what not instead of text completion algorithms.
- avogt27 1y agoIt's really a bummer to see this marketed as 'AI Discovers Something New'. The authors in the actual paper carried out an enormous amount of work, the vast majority of which is relatively standard biochemistry and cell biology - nothing to do with computational techniques. The AlphaFold3 analysis (the AI contribution) literally accounts for a few panels in a supplementary figure - it didn't even help guide their choice of small molecule inhibitors since those were already known. AlphaFold (among other related tools) is absolutely a game changer in structural biology and biophysics, but this is a pretty severe case of AI hype overshadowing the real value of the work.
- SwtCyber 1y agoHonestly, the fact that the core discovery still relied so heavily on classic biochemistry and experimental validation actually makes it even more impressive to me
- 0x70run 1y agoWish I could upvote this more!
- frizlab 1y agoWhen I read the title of the article in my RSS feed my first instinct was to go straight to here with a snarky “How was it not actually AI that did this?” in my head… As usual I was not disappointed.
- bilekas 1y agoYeah it’s a really strange title for the actual work, it’s like saying bic pens helped find x y z simply because they used them to take notes.
- tim333 1y ago>“It really demanded modern AI to formulate the three-dimensional structure very precisely to make this discovery.” It's not like bic pens. It's a new technique they couldn't do before that helped crack the mystery. Also the title is "AI Helps..." not "AI Discovers" so that's kind of a strawman. I don't think anyone is denying the humans did great work. Maybe it's more like Joe Boggs uses the Hubble telescope to find a new galaxy and moaning because the telescope gets a mention. I'm quite enthusiastic about the AI bit. My grandad died with alzheimer's 50 years ago. My sister is due to die of als in a couple of years. Both areas have been kind of stuck for decades. I'm hoping the AI modeling allows some breakthroughs.
- jasonkester 1y agoI notice that I have a form of Gell-Mann amnesia for this sort of thing. Do we need a new term, or does that cover it? Because I find myself nodding along with optimism, having two grandfathers that died from this disease. It’d be great if something could sift through all the data and come up with a novel solution. Then I remember that this is the same technology that eagerly tries to autocomplete every other line of my code to include two nonexistent variables and a nonexistent function. I hope this field has some good people to sanity check this stuff.
- bitwize 1y ago"I was optimistic when my friend told me about his new hammer and how much it helped him assemble a cabinet he was working on. Then I remember that this is the same technology that failed to drive in screws for a project I was working on a week ago." The AI that's being used in applications like this is not generative AI. It really is just "sparkling statistics" and it's tremendously useful in applications like this because it can accelerate the finding of patterns in data that form the basis of new discoveries.
- xyst 1y agoThe author here is shoehorning "AI" into the headline to boost views. Quite misleading. "AI" in this case was used to generate a 3D model of a protein. Literally, something you can grab from Wikipedia — https://en.m.wikipedia.org/wiki/Phosphoglycerate_dehydrogenase https://en.m.wikipedia.org/wiki/Phosphoglycerate_dehydrogena... The underlying work performed by the researchers is much more interesting — https://linkinghub.elsevier.com/retrieve/pii/S0092867425003976 https://linkinghub.elsevier.com/retrieve/pii/S00928674250039... They identified a possible upstream pathway that could help treat disease and build therapeutic treatments for Alzheimer’s. I don’t know about you all but I’m tired of the AI-mania. At least author didn’t but "blockchain" in the article.
- SwtCyber 1y agoCurious to see how this line of research evolves, especially once they get into clinical trials
- dsign 1y agoThis piece of the puzzle, and its finding, if confirmed, is very neat. But I think we are barking at the wrong tree, because senescence is inherently chaotic. Sometimes we identify a disease with a set of common symptoms because there are many alternative causes that lead to those very symptoms. It's like "convergent symptoms", so to speak. If I had any funding to work freely in these subjects, I would instead focus on the more fundamental questions of computationally mapping and reversing cellular senescence, starting with something tiny and trivial (but perhaps not tiny nor trivial enough) like a rotifer. My focus wouldn't be the biologists' "we want to understand this rotifer", "or we want to understand senescence", but more "can we create an exact computational framework to map senescence, a framework which can be extended and applied to other organisms"? Sadly, funding for science is a lost cause, because even where/when it is available, it comes with all sort of political and ideological chains.
- po 1y agoHave you ever lived with or helped a person with AD? It's not cellular senescence. What you're talking about is fine and well, but AD is a devastating disease that has very particular symptoms. We may not know all of the causes, but reversing cellular senescence isn't going to solve this. Researching and curing AD is not barking up the wrong tree. There is a horrible deadly monster in that tree that needs defeating. I hope people also get scientific funding for other age-related issues.
- tim333 1y agoThere's a lot of interesting research going on in cellular reprogramming to make cells seem younger. See for example https://www.washingtonpost.com/wellness/2025/03/06/cellular-reprogramming-longevity-reverse-aging/ https://www.washingtonpost.com/wellness/2025/03/06/cellular-...
- yapyap 1y agoAI steals credit for unraveling a cause of Alzheimers so the bubble will exist a bit longer
- gaopeng860330 1y ago[dead]
- cdf 1y agoI always believed that the AI/LLM/ML hysteria is misapplied to software engineering... it just happens to be a field adjacent to it, but not one that can very well apply it. Medicine and Law, OTOH, suffers heavily from a fractal volume of data and a dearth of experts who can deal with the tedium of applying an expert eye to this much data. Imagine we start capturing ultrasound and chest xrays en masse, or giving legal advice for those who needs help. LLMs/ML are more likely to get this right, than writing computer code.
- hermitShell 1y ago100% agree ‘chat bots’ will not be a revolutionary technology, but other uses of the underlying technology will be. General robotics, pharmaceuticals, new matter… and eventually 1st line medicines and law sure, but I sure don’t want doctors to vibe diagnose me, or lawmakers to vibe legislate.
- IX-103 1y ago[Insert "let me laugh even harder" meme here] That would be actual malpractice in either case. LLMs have a history of fabricating laws and precedents when acting as a lawyer. Any advice from the LLM would likely be worse than just assuming something sensible, as that is more likely to reflect what the law is than what the LLM hallucinates it to be. Medicine is in many ways similar. As for your suggestion to be capture and analyze ultrasounds and X-rays en-mass, that would be malpractice even if it were performed by an actual Doctor instead of an AI. We don't know the base rate of many benign conditions, except that they are always higher than we expect. The additional images are highly likely to show conditions that could be either benign or dangerous, and additional procedures (such as biopsies) would be needed to determine which it is. This would create additional anxiety in patients from the possible diagnosis and further pain and possible complications from the additional procedures. While you could argue for taking these images and not acting on them, you would either tell the patients the results and leave them worried about what the discovered masses are (so they likely will have the procedures anyway) or you won't tell them (which has ethical implications). Good luck getting that past the institutional review board.
- discodonkey 1y ago
- codr7 1y agoIt's a hell of a lot more likely to find the primary causes of Alzheimers outside of the human body imo, medicines/pollution/additives/radiation etc. The human body is a pretty amazing construction, nature doesn't make a lot of mistakes.
- mihalycsaba 1y agoIt makes a lot of mistakes. Without modern medicine we wouldn't live this long. Alzheimer's is not a modern disease.
- hello_computer 1y agoThe primary improvement to human life expectancy was not medicine, but public sanitation. Prior to that, death was bi-modal, with peaks at infancy and old age. When people (and doctors) started washing their hands, the infant peak was flattened. Dead toddlers really kick the average in the nuts.
- hello_computer 1y agoThere is a strong correlation (noting my word choice here before the incorrectors accuse me of confusing it with causation) between general anesthesia and onset of dementia. I’m not going to dig it up, but it is easy enough to find on pubmed. There is a decent amount of noticing in the literature.
- netdevphoenix 1y agoThe 202x trend of adding AI into every story when is irrelevant is getting tiresome
- dudeinjapan 1y agoIf AI causes us humans to workout our brains less, maybe it is also causing Alzheimer's. In the words of Homer Simpson: "To alcohol! The cause of--and solution to--all life's problems." https://www.youtube.com/watch?v=SXyrYMxa-VI https://www.youtube.com/watch?v=SXyrYMxa-VI
- psyclobe 1y agoA little to late for my mom, but maybe it will help me in the future...
- maggiepatells42 1y ago[dead]