4 ms·

NFT and Abeta are part of the traditional AD diagnosis. NFT studies have seen no lack of funding. But for the record, I do think tau plays a role. I'm not sold

NFT and Abeta are part of the traditional AD diagnosis. NFT studies have seen no lack of funding. But for the record, I do think tau plays a role. I'm not sold either way on ABeta or Tau (maybe both). "synapse loss" is a better correlate for dementia because, obviously. But synapse loss is the outcome of the disease, not the cause of the disease.

nabla9 4y ago
The point is that evidence for amyloid-hypothesis is near non-existent unless you take it as a starting point and do circular reasoning. In clinical trials patients who show the biggest decrease in brain amyloid or tau are not correlated at all with any particular clinical improvement (small as they are). In mice you can prevent amyloids but don't prevent the disease.
- subroutine 4y ago
  And your big brain idea is that it's all about the tangles not the plaques (but not NF tangles from tau mechanisms; it's actually hard to tell because the alt hypothesis you cited above basically say that it's not diffuse Abeta and NTF, instead it's ABeta and NFT inside neurons.
  - nabla9 4y ago
    We just don't know. The previous big brain idea just did not pan out.
    - subroutine 4y ago
      I don't think mixed results from one or two clinical trials warrants a total pivot (see my first post). But, again, I'm not opposed to exploring novel avenues. Anyone who lives long enough will get dementia, so both broad and deep insights are certainly welcome.
      - nabla9 4y ago
        > from one or two clinical trials warrants From one or two?? Cognitive outcomes of anti-amyloid-β monoclonal antibodies in patients with Alzheimer's disease: A systematic review and meta-analysis of randomized controlled trials https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.057778 https://alz-journals.onlinelibrary.wiley.com/doi/full/10.100... Had Enough, Eh? Come Back and Take What's Coming to You! https://www.science.org/content/blog-post/had-enough-eh https://www.science.org/content/blog-post/had-enough-eh
        subroutine 4y ago
        Ok, there's more than I knew about. "We found 12 eligible studies in 443 identified records, involving 6736 patients, mean age 71.4 ± 2. We found a small benefit in cognitive outcomes in patients treated with Aβ-mAbs." So there's a small benefit to using antibody treatment. To me suggests that Abeta is a good target, but antibodies are not a sufficient Rx. Have you seen a brain at BRAAK stage 4-6?

nabla9 4y ago

The point is that evidence for amyloid-hypothesis is near non-existent unless you take it as a starting point and do circular reasoning. In clinical trials patients who show the biggest decrease in brain amyloid or tau are not correlated at all with any particular clinical improvement (small as they are). In mice you can prevent amyloids but don't prevent the disease.

subroutine 4y ago
And your big brain idea is that it's all about the tangles not the plaques (but not NF tangles from tau mechanisms; it's actually hard to tell because the alt hypothesis you cited above basically say that it's not diffuse Abeta and NTF, instead it's ABeta and NFT inside neurons.
- nabla9 4y ago
  We just don't know. The previous big brain idea just did not pan out.
  - subroutine 4y ago
    I don't think mixed results from one or two clinical trials warrants a total pivot (see my first post). But, again, I'm not opposed to exploring novel avenues. Anyone who lives long enough will get dementia, so both broad and deep insights are certainly welcome.
    - nabla9 4y ago
      > from one or two clinical trials warrants From one or two?? Cognitive outcomes of anti-amyloid-β monoclonal antibodies in patients with Alzheimer's disease: A systematic review and meta-analysis of randomized controlled trials https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.057778 https://alz-journals.onlinelibrary.wiley.com/doi/full/10.100... Had Enough, Eh? Come Back and Take What's Coming to You! https://www.science.org/content/blog-post/had-enough-eh https://www.science.org/content/blog-post/had-enough-eh
      - subroutine 4y ago
        Ok, there's more than I knew about. "We found 12 eligible studies in 443 identified records, involving 6736 patients, mean age 71.4 ± 2. We found a small benefit in cognitive outcomes in patients treated with Aβ-mAbs." So there's a small benefit to using antibody treatment. To me suggests that Abeta is a good target, but antibodies are not a sufficient Rx. Have you seen a brain at BRAAK stage 4-6?