7 ms·

> …small amounts of clumping tau protein in the brain and cerebrospinal fluid, which lead to Alzheimer's disease. I don’t think this should be stated as a prov

by glaugh 2y ago

> …small amounts of clumping tau protein in the brain and cerebrospinal fluid, which lead to Alzheimer's disease. I don’t think this should be stated as a proven fact anymore, given the doubt now cast over the amyloid hypothesis This is a nice summary of the case: https://podcasts.apple.com/us/podcast/plain-english-with-derek-thompson/id1594471023?i=1000691074414 https://podcasts.apple.com/us/podcast/plain-english-with-der...

im3w1l 2y ago
I've seen this point brought up many times over the years and yet research in this direction seems to continue, so I think there must be more to it. I asked chatgpt about it, and it claims that the controversial paper was influential but it was more about a certain sub-hypothesis that got called into question after that rather than the entire thing. Now I know that bringing up chatgpt is frowned upon here but I thought I should make an exception for this case as its not so easy for me to answer otherwise.
- robwwilliams 2y ago
  You might enjoy “How Not To Study A Disease: The Story of Alzheimer’s” by Karl Herrup (2023, MIT Press). Great sad overview of the hegemony of the Abeta hypothesis that now has a Tau hypothesis buddy. https://mitpress.mit.edu/9780262546010/how-not-to-study-a-disease/ https://mitpress.mit.edu/9780262546010/how-not-to-study-a-di...
robwwilliams 2y ago
Agree strongly with you. This statement make Alzheimer’s into a wonderfully “simple” monogenic disease like Huntington’s but all age-related disease have many complex interwoven weaker and stronger causes—-even Huntington’s disease in which the same mutation type (numbers of CAG mutations in neurons) can cause symptoms over a 20 year range. Too bad that headlines are inherently short and sometimes misleading. Simple sells.
pedalpete 2y ago
The problem with the amyloid hypothesis is most likely not that it is wrong, but that it is incomplete, and I would say that is the problem with this test as well. I work in neurotech/sleeptech, and AD researchers are using (or want to use) slow-wave enhancement to prevent and possibly manage AD. However, the test for AD is still a psychological tests along with neuroimaging to look for tau tangles and amyloid plaque build up. It has been discussed that we may be looking at multiple different diseases which have similar symptoms and without completely understanding the disease itself, we are categorizing them as AD, though they may have different pathways. Though we can't ignore the challenges to the amyloid hypothesis, we also shouldn't completely throw it out. Most of the experts I've spoken with still believe it is the best hypothesis we have, but that we also should not ignore other possibilities.
- tim333 2y ago
  It surprises me that some obvious clues to treatment are passed over as I guess they don't fit the politics? Like >A team of researchers in Jerusalem, he says, decided to look at patients who survived bladder cancer and compare dementia prevalence among patients treated with BCG and those who weren’t. “Do they differ in the rate at which they get Alzheimer’s disease?” The answer is yes – the BCG group appeared to get 75% protection against Alzheimer’s. A number of studies have now found varying levels of protection from BCG, with an average, according to one meta‑analysis, of 45%. There's a lot of evidence a lot of it is set off by infectious microbes which can be treated in the usual way. (From https://www.theguardian.com/lifeandstyle/2024/dec/01/the-brain-microbiome-could-understanding-it-help-prevent-dementia?lid=unhn64q4wvgg https://www.theguardian.com/lifeandstyle/2024/dec/01/the-bra...) The 'politics' puzzles me. Maybe the head of department got fame for hypothesis A and feels his power or money is threatened by hypothesis B? It's not what science should be about. (There was an entertaining angry Sabine Hossenfelder youtube a few minutes ago on the corruption of science just wasting money, but really letting people die of Alzheimer's is worse. https://youtu.be/shFUDPqVmTg https://youtu.be/shFUDPqVmTg)
  - manmal 2y ago
    There‘s also a weird relation with the oral microbiome. Probably not that surprising, seeing how much translocation is actually happening between our microbiomes. Just an n=1 ofc, but someone in my family got all their remaining teeth pulled and replaced with implants, and afterwards, within 3 years went from asymptomatic to dead from AD. The progression was mind boggling. I‘ve wondered for a long time whether the oral work was related to this - the surgery caused so much damage that it certainly exceeded capacity to heal, opening the doors wide for any pathogens.
swores 2y ago
Is it not still the case that they do correlate, and therefore the article talking about them as biomarkers is not making the mistake you think it is (as if it was talking about them as the thing to get rid of to prevent Alzheimer's)? Because "lead to" is not the same as "causes". Or has latest research shown that even a non-causal link should be dismissed?
- kadoban 2y ago
  "Lead to" is a synonym for "causes".
  - swores 2y ago
    It can be used that way, but not always. In fact, traditionally your way is the less common usage. A path of breadcrumbs leads to the gingerbread house, despite the house not existing because of the path (or a road leading to a house, to get away from witches). Unless you mean that in medical research it's universally agreed to only use it in that way? I'm sceptical that's the case but could be convinced... (Either way, "lead to" obviously isn't at all clear enough if they did intend to mean "points towards, without causation".)
    - kadoban 2y ago
      "Lead to" physically, in terms of locations, means that, but I have never heard it mean "preceeds" and not "causes" in terms of events. Yeah, I think they worded it incorrectly.
- dimal 2y ago
  Ok “lead to” might not be exactly equivalent to “causes”, but it’s not even accurate because tau doesn’t ALWAYS lead to Alzheimer’s. The correlation is not strong. People have tau and no Alzheimer’s and other people have Alzheimer’s symptoms and no tau. So what good does it do you to test for tau? It’s a higher probability of Alzheimer’s, but not nearly definitive. I suspect that if this test is productized, this nuance will be lost on many doctors. Seems like a good test to give someone so you can scare them into taking a drug that also has very little evidence of effectiveness.

by glaugh 2y ago

im3w1l 2y ago

I've seen this point brought up many times over the years and yet research in this direction seems to continue, so I think there must be more to it. I asked chatgpt about it, and it claims that the controversial paper was influential but it was more about a certain sub-hypothesis that got called into question after that rather than the entire thing. Now I know that bringing up chatgpt is frowned upon here but I thought I should make an exception for this case as its not so easy for me to answer otherwise.

robwwilliams 2y ago
You might enjoy “How Not To Study A Disease: The Story of Alzheimer’s” by Karl Herrup (2023, MIT Press). Great sad overview of the hegemony of the Abeta hypothesis that now has a Tau hypothesis buddy. https://mitpress.mit.edu/9780262546010/how-not-to-study-a-disease/ https://mitpress.mit.edu/9780262546010/how-not-to-study-a-di...

robwwilliams 2y ago

Agree strongly with you. This statement make Alzheimer’s into a wonderfully “simple” monogenic disease like Huntington’s but all age-related disease have many complex interwoven weaker and stronger causes—-even Huntington’s disease in which the same mutation type (numbers of CAG mutations in neurons) can cause symptoms over a 20 year range. Too bad that headlines are inherently short and sometimes misleading. Simple sells.

pedalpete 2y ago

The problem with the amyloid hypothesis is most likely not that it is wrong, but that it is incomplete, and I would say that is the problem with this test as well. I work in neurotech/sleeptech, and AD researchers are using (or want to use) slow-wave enhancement to prevent and possibly manage AD. However, the test for AD is still a psychological tests along with neuroimaging to look for tau tangles and amyloid plaque build up. It has been discussed that we may be looking at multiple different diseases which have similar symptoms and without completely understanding the disease itself, we are categorizing them as AD, though they may have different pathways. Though we can't ignore the challenges to the amyloid hypothesis, we also shouldn't completely throw it out. Most of the experts I've spoken with still believe it is the best hypothesis we have, but that we also should not ignore other possibilities.

tim333 2y ago
It surprises me that some obvious clues to treatment are passed over as I guess they don't fit the politics? Like >A team of researchers in Jerusalem, he says, decided to look at patients who survived bladder cancer and compare dementia prevalence among patients treated with BCG and those who weren’t. “Do they differ in the rate at which they get Alzheimer’s disease?” The answer is yes – the BCG group appeared to get 75% protection against Alzheimer’s. A number of studies have now found varying levels of protection from BCG, with an average, according to one meta‑analysis, of 45%. There's a lot of evidence a lot of it is set off by infectious microbes which can be treated in the usual way. (From https://www.theguardian.com/lifeandstyle/2024/dec/01/the-brain-microbiome-could-understanding-it-help-prevent-dementia?lid=unhn64q4wvgg https://www.theguardian.com/lifeandstyle/2024/dec/01/the-bra...) The 'politics' puzzles me. Maybe the head of department got fame for hypothesis A and feels his power or money is threatened by hypothesis B? It's not what science should be about. (There was an entertaining angry Sabine Hossenfelder youtube a few minutes ago on the corruption of science just wasting money, but really letting people die of Alzheimer's is worse. https://youtu.be/shFUDPqVmTg https://youtu.be/shFUDPqVmTg)
- manmal 2y ago
  There‘s also a weird relation with the oral microbiome. Probably not that surprising, seeing how much translocation is actually happening between our microbiomes. Just an n=1 ofc, but someone in my family got all their remaining teeth pulled and replaced with implants, and afterwards, within 3 years went from asymptomatic to dead from AD. The progression was mind boggling. I‘ve wondered for a long time whether the oral work was related to this - the surgery caused so much damage that it certainly exceeded capacity to heal, opening the doors wide for any pathogens.

swores 2y ago

Is it not still the case that they do correlate, and therefore the article talking about them as biomarkers is not making the mistake you think it is (as if it was talking about them as the thing to get rid of to prevent Alzheimer's)? Because "lead to" is not the same as "causes". Or has latest research shown that even a non-causal link should be dismissed?

kadoban 2y ago
"Lead to" is a synonym for "causes".
- swores 2y ago
  It can be used that way, but not always. In fact, traditionally your way is the less common usage. A path of breadcrumbs leads to the gingerbread house, despite the house not existing because of the path (or a road leading to a house, to get away from witches). Unless you mean that in medical research it's universally agreed to only use it in that way? I'm sceptical that's the case but could be convinced... (Either way, "lead to" obviously isn't at all clear enough if they did intend to mean "points towards, without causation".)
  - kadoban 2y ago
    "Lead to" physically, in terms of locations, means that, but I have never heard it mean "preceeds" and not "causes" in terms of events. Yeah, I think they worded it incorrectly.
dimal 2y ago
Ok “lead to” might not be exactly equivalent to “causes”, but it’s not even accurate because tau doesn’t ALWAYS lead to Alzheimer’s. The correlation is not strong. People have tau and no Alzheimer’s and other people have Alzheimer’s symptoms and no tau. So what good does it do you to test for tau? It’s a higher probability of Alzheimer’s, but not nearly definitive. I suspect that if this test is productized, this nuance will be lost on many doctors. Seems like a good test to give someone so you can scare them into taking a drug that also has very little evidence of effectiveness.