3 ms·

The Amyloid hypothesis persisted for so long because we didn't have any obvious counterarguments since it is so hard to do studies on the brain. Which also mea

by bsder 6mo ago

The Amyloid hypothesis persisted for so long because we didn't have any obvious counterarguments since it is so hard to do studies on the brain. Which also means that it's not a bad hypothesis. What happened is we got the tools to start studying viral associations with other diseases and ... whooops ... suddenly there are associations. The shingles and RSV vaccines seem to affect dementia while others like influenza don't. Now people can ask questions about why those particular vaccines affect dementia while others don't. And suddenly we have falsifiable tests. Now we can subject all hypotheses (including Amyloid) to stronger scrutiny.

ramraj07 6mo ago
There were no cointerarguments? There was a very simple counterargument: where was the causal data? If none exist why should I counter argue when you hadn't proven it to begin with.
- bsder 6mo ago
  There is a LOT of causal data. Autopsies of brains of Alzheimer's patients were rife with amyloid. People with mutations that caused amyloid got Alzheimer's earlier than others. The hypothesis didn't come from nowhere. To contrast, look at how much trouble medicine has had treating brain tumors. It has taken a long time to get effective treatments for various reasons. And Alzheimer's is way less direct in cause/effect.
  - ramraj07 6mo ago
    > Autopsies of brains of Alzheimer's patients were rife with amyloid Do you want think carefully about how this can possibly suggest this is a causal link? > People with mutations that caused amyloid got Alzheimer's earlier than others. People with mutations in those genes got a particular type of inherited alzheimers early, this says nothing about the cause of general Alzheimers.
    - stackghost 6mo ago
      This comment is so needlessly aggressive and argumentative. I hate this about HN
      - deleted 6mo ago
        [deleted]
      - curiousObject 6mo ago
        It is sad. That reply, which you rightfully were irritated by, could have been expressed as a polite question. That sort of question is what the response from user @bsder above helpfully tries to answer. That mode would invite more productive discussion, not more defensive annoyance. Rules on HN say “Be kind. Don't be snarky. Converse curiously; don't cross-examine. Edit out swipes.” but it is hard. All I can suggest is: be patient and try to be positive
      - i000 6mo ago
        It is also wrong...
        ramraj07 6mo ago
        Wouldn't mind knowing how.
      - shermantanktop 6mo ago
        It’s the way one talks to an LLM which has made a mistake.
    - bsder 6mo ago
      > People with mutations in those genes got a particular type of inherited alzheimers early, this says nothing about the cause of general Alzheimers. This is completely analogous to claiming that people with mutations in BRCA (which causes a lot of early breast cancers) says nothing about general "cancer". That's simply flat-out wrong. Genetic mutations like BRCA affect certain subsystems and many of those subsystems are common and relevant to many different cancers outside of breast cancer or breast cancers that appear later. Lots and lots of cancer research proceeded by studying the common systems that BRCA affects. Sure, those subsystems aren't involved in every cancer, but they're involved in a solid chunk of them. And, even better, when you find one that isn't affected by one of those subsystems that BRCA touches, that's an interesting result, too. Now you can look at what the differences are, figure out what the new subsystems are and categorize your cancer more specifically which makes successful treatment more likely. There is absolutely no reason to believe that Alzheimer's is any different on that front.
- bglazer 6mo ago
  Ah causal data! It’s a shame none of the scientists or statisticians thought of getting causal data. How would we get that? Well maybe we could just inject amyloid into a person’s brain. Or simply remove all the amyloid from a person’s brain. That should do it, right? I mean an amyloid injection is wildly unethical and it’s also not the natural progression of Alzheimer’s. Removing amyloid is a simple matter of investing billions of dollars into drug development. Also how do you tell whether that was actually “causal” if the patients improve after plaque removal. I mean come on, you have to work the evidence and the experimental tools that we actually have. This kind of epistemic puritanism doesn’t help anyone.
  - bsder 6mo ago
    > Well maybe we could just inject amyloid into a person’s brain. Erm, we kinda did? People who got cadaver-derived human growth hormone from Alzheimer's patients got Alzheimer's. https://www.nature.com/articles/s41591-023-02729-2 https://www.nature.com/articles/s41591-023-02729-2 And we just had an actual autopsy confirm a case: https://www.medscape.com/viewarticle/new-evidence-strengthens-case-iatrogenic-alzheimers-2026a1000ah9 https://www.medscape.com/viewarticle/new-evidence-strengthen...
tim333 6mo ago
An obvious counter hypothesis is the amyloid is produced to counter an infectious agent. It is a reaction to that, not the cause. I think HSV-1 has been hypothesised. I'm not that up on it, just saying there are alternatives.
- XorNot 6mo ago
  Which is only relevant if you actually find an infectious agent doing something in the right place, which so far we have not. The vaccine prevention connection for example AFAIK is just pure statistics: you get the shingles vaccine, your population level Alzheimer's risk drops but we have no direct evidence of why this should be. Its entirely possible we later find it has no effect and it's a population level quirk of people who were likely to get a shingles vaccine until that research - conversely the cost of just getting one is incredibly low (hence why I did, in relation to that exact data).

by bsder 6mo ago

ramraj07 6mo ago

There were no cointerarguments? There was a very simple counterargument: where was the causal data? If none exist why should I counter argue when you hadn't proven it to begin with.

bsder 6mo ago
There is a LOT of causal data. Autopsies of brains of Alzheimer's patients were rife with amyloid. People with mutations that caused amyloid got Alzheimer's earlier than others. The hypothesis didn't come from nowhere. To contrast, look at how much trouble medicine has had treating brain tumors. It has taken a long time to get effective treatments for various reasons. And Alzheimer's is way less direct in cause/effect.
- ramraj07 6mo ago
  > Autopsies of brains of Alzheimer's patients were rife with amyloid Do you want think carefully about how this can possibly suggest this is a causal link? > People with mutations that caused amyloid got Alzheimer's earlier than others. People with mutations in those genes got a particular type of inherited alzheimers early, this says nothing about the cause of general Alzheimers.
  - stackghost 6mo ago
    This comment is so needlessly aggressive and argumentative. I hate this about HN
    - deleted 6mo ago
      [deleted]
    - curiousObject 6mo ago
      It is sad. That reply, which you rightfully were irritated by, could have been expressed as a polite question. That sort of question is what the response from user @bsder above helpfully tries to answer. That mode would invite more productive discussion, not more defensive annoyance. Rules on HN say “Be kind. Don't be snarky. Converse curiously; don't cross-examine. Edit out swipes.” but it is hard. All I can suggest is: be patient and try to be positive
    - i000 6mo ago
      It is also wrong...
      - ramraj07 6mo ago
        Wouldn't mind knowing how.
    - shermantanktop 6mo ago
      It’s the way one talks to an LLM which has made a mistake.
  - bsder 6mo ago
    > People with mutations in those genes got a particular type of inherited alzheimers early, this says nothing about the cause of general Alzheimers. This is completely analogous to claiming that people with mutations in BRCA (which causes a lot of early breast cancers) says nothing about general "cancer". That's simply flat-out wrong. Genetic mutations like BRCA affect certain subsystems and many of those subsystems are common and relevant to many different cancers outside of breast cancer or breast cancers that appear later. Lots and lots of cancer research proceeded by studying the common systems that BRCA affects. Sure, those subsystems aren't involved in every cancer, but they're involved in a solid chunk of them. And, even better, when you find one that isn't affected by one of those subsystems that BRCA touches, that's an interesting result, too. Now you can look at what the differences are, figure out what the new subsystems are and categorize your cancer more specifically which makes successful treatment more likely. There is absolutely no reason to believe that Alzheimer's is any different on that front.
bglazer 6mo ago
Ah causal data! It’s a shame none of the scientists or statisticians thought of getting causal data. How would we get that? Well maybe we could just inject amyloid into a person’s brain. Or simply remove all the amyloid from a person’s brain. That should do it, right? I mean an amyloid injection is wildly unethical and it’s also not the natural progression of Alzheimer’s. Removing amyloid is a simple matter of investing billions of dollars into drug development. Also how do you tell whether that was actually “causal” if the patients improve after plaque removal. I mean come on, you have to work the evidence and the experimental tools that we actually have. This kind of epistemic puritanism doesn’t help anyone.
- bsder 6mo ago
  > Well maybe we could just inject amyloid into a person’s brain. Erm, we kinda did? People who got cadaver-derived human growth hormone from Alzheimer's patients got Alzheimer's. https://www.nature.com/articles/s41591-023-02729-2 https://www.nature.com/articles/s41591-023-02729-2 And we just had an actual autopsy confirm a case: https://www.medscape.com/viewarticle/new-evidence-strengthens-case-iatrogenic-alzheimers-2026a1000ah9 https://www.medscape.com/viewarticle/new-evidence-strengthen...

tim333 6mo ago

An obvious counter hypothesis is the amyloid is produced to counter an infectious agent. It is a reaction to that, not the cause. I think HSV-1 has been hypothesised. I'm not that up on it, just saying there are alternatives.

XorNot 6mo ago
Which is only relevant if you actually find an infectious agent doing something in the right place, which so far we have not. The vaccine prevention connection for example AFAIK is just pure statistics: you get the shingles vaccine, your population level Alzheimer's risk drops but we have no direct evidence of why this should be. Its entirely possible we later find it has no effect and it's a population level quirk of people who were likely to get a shingles vaccine until that research - conversely the cost of just getting one is incredibly low (hence why I did, in relation to that exact data).