4 ms·

Have a look at the comments on this post and let me know what you think after that. https://www.alzforum.org/news/community-news/sylvain-lesne-who-found-av56-ac

Have a look at the comments on this post and let me know what you think after that. https://www.alzforum.org/news/community-news/sylvain-lesne-who-found-av56-accused-image-manipulation https://www.alzforum.org/news/community-news/sylvain-lesne-w... Starting with just Dr. Ashe's comment at the top: > Based on my published work (Liu et al., 2015; Ashe, 2020), it is clear that there are two general forms of Aβ, type 1 and type 2. One particular form of type 1 (referred to in our papers as Aβ*56 and in the Science article as “toxic oligomers”) was shown by my lab and others to impair memory function in mice. The type 2 form of Aβ is the one found in amyloid plaques. It is this latter form that drug developers have repeatedly but unsuccessfully targeted. There have been no clinical trials targeting the type 1 form of Aβ, the form which my research has suggested is more relevant to dementia. Mr. Piller erroneously conflated the two forms of Aβ. There's a lot of interesting comments after Ashe's as well.

ncmncm 4y ago
I read through all of the comments before I posted, as I noted: "what I got from the comments there" and "all the comments posted in response to the fraud...". Assuming I lied about that violates HN guidelines. Too. A careful reading shows Ashe is still talking about mouse amyloids, i.e., something never shown, over decades and $billions, to have anything to do with how Alzheimer's develops in humans. There is plenty of failure and blame to go around. They clearly don't need your help dodging it. And you did not answer, or even address, any of my questions.
- civilized 4y ago
  Dismissing mouse models is silly. Lots of successful medical research has turned on evidence from mouse models. Any Alzheimer's research paradigm you prefer will use them too if pursued seriously. I don't know if anything amyloid beta will pan out, but none of your statements or questions seem to illuminate the matter at all. They seem loaded with unevidenced presupposition. And I don't track your comments about what you've read or not read, only whether the comments seem to reflect knowledge from the reading. I would like the discussion to be informed by the experts, so I brought in the experts. That's all there is to it.
  - ncmncm 4y ago
    That is very far from all there is to it. You leveled accusations at me, in direct violation of HN guidelines, that misrepresented what I said and did. Mouse models are of course used throughout medical research. There is a sizeable literature on correct use of mouse models. Alzheimer's researchers have, very clearly, wholly ignored them. Probably the most central requirement of use of mouse models is demonstrating that they have something concrete to do with the illness modeled, something that in decades they have not bothered with. Your noisy defense of people who have manifestly wasted tens of $billions of taxpayers' money over decades is based on nothing.
    - civilized 4y ago
      > Alzheimer's researchers have, very clearly, wholly ignored them This is more of what I was talking about - the extreme confidence that seems to require no externally demonstrated evidence or expert knowledge. It's clear that in continuing this discussion I can expect only doubling down on these armchair certainties. Incidentally, even the paradigm-challenging researchers are using mouse models and amyloid plaques to make their arguments, e.g. Dr. Itzhaki's work on HSV as a risk factor [1]. Broadsides against these things sweep away the very work you wish to promote. > Your noisy defense I'm not defending amyloid beta stuff. I don't know enough to say one way or another, and we should probably invest in diverse approaches when focusing on just one isn't working out very well. That said, I think that challenges to the scientific experts should be based on compelling evidence and reasoning, not mere assertions of certainty. > misrepresented what I said and did People can look at the conversation and decide that for themselves. I tried to tell you something that would help you have a more meaningful intellectual life if you understood it. Now you've heard it. You won't hear from me again. Good day. [1] https://www.statnews.com/2019/06/25/alzheimers-cabal-thwarted-progress-toward-cure/ https://www.statnews.com/2019/06/25/alzheimers-cabal-thwarte...

ncmncm 4y ago

I read through all of the comments before I posted, as I noted: "what I got from the comments there" and "all the comments posted in response to the fraud...". Assuming I lied about that violates HN guidelines. Too. A careful reading shows Ashe is still talking about mouse amyloids, i.e., something never shown, over decades and $billions, to have anything to do with how Alzheimer's develops in humans. There is plenty of failure and blame to go around. They clearly don't need your help dodging it. And you did not answer, or even address, any of my questions.

civilized 4y ago
Dismissing mouse models is silly. Lots of successful medical research has turned on evidence from mouse models. Any Alzheimer's research paradigm you prefer will use them too if pursued seriously. I don't know if anything amyloid beta will pan out, but none of your statements or questions seem to illuminate the matter at all. They seem loaded with unevidenced presupposition. And I don't track your comments about what you've read or not read, only whether the comments seem to reflect knowledge from the reading. I would like the discussion to be informed by the experts, so I brought in the experts. That's all there is to it.
- ncmncm 4y ago
  That is very far from all there is to it. You leveled accusations at me, in direct violation of HN guidelines, that misrepresented what I said and did. Mouse models are of course used throughout medical research. There is a sizeable literature on correct use of mouse models. Alzheimer's researchers have, very clearly, wholly ignored them. Probably the most central requirement of use of mouse models is demonstrating that they have something concrete to do with the illness modeled, something that in decades they have not bothered with. Your noisy defense of people who have manifestly wasted tens of $billions of taxpayers' money over decades is based on nothing.
  - civilized 4y ago
    > Alzheimer's researchers have, very clearly, wholly ignored them This is more of what I was talking about - the extreme confidence that seems to require no externally demonstrated evidence or expert knowledge. It's clear that in continuing this discussion I can expect only doubling down on these armchair certainties. Incidentally, even the paradigm-challenging researchers are using mouse models and amyloid plaques to make their arguments, e.g. Dr. Itzhaki's work on HSV as a risk factor [1]. Broadsides against these things sweep away the very work you wish to promote. > Your noisy defense I'm not defending amyloid beta stuff. I don't know enough to say one way or another, and we should probably invest in diverse approaches when focusing on just one isn't working out very well. That said, I think that challenges to the scientific experts should be based on compelling evidence and reasoning, not mere assertions of certainty. > misrepresented what I said and did People can look at the conversation and decide that for themselves. I tried to tell you something that would help you have a more meaningful intellectual life if you understood it. Now you've heard it. You won't hear from me again. Good day. [1] https://www.statnews.com/2019/06/25/alzheimers-cabal-thwarted-progress-toward-cure/ https://www.statnews.com/2019/06/25/alzheimers-cabal-thwarte...