6 ms·

Virus and Two Types of Bacteria as Major Causes of Alzheimer’s

149 points by musha68k 10y ago

officialjunk 10y ago
From the abstract towards the bottom of the page: > We refer to the many studies, mainly on humans, implicating specific microbes in the elderly brain, notably herpes simplex virus type 1 (HSV1), Chlamydia pneumoniae, and several types of spirochaete, in the etiology of AD.
jonny_eh 10y ago
This is from March. Any critiques published?
- cpncrunch 10y ago
  https://www.washingtonpost.com/news/speaking-of-science/wp/2016/03/14/calm-down-herpes-probably-isnt-going-to-give-you-alzheimers/ https://www.washingtonpost.com/news/speaking-of-science/wp/2...
MrQuincle 10y ago
You probably have herpes but that's okay: https://www.washingtonpost.com/news/speaking-of-science/wp/2016/03/14/calm-down-herpes-probably-isnt-going-to-give-you-alzheimers/ https://www.washingtonpost.com/news/speaking-of-science/wp/2... My wife studies Alzheimer's and I hope she will respond here, but I'm afraid she gets too angry by sensationalist stories based on editorials rather than mainline research. Of course there is inflammation involved. From what I understand talking with her, there is not much mechanistic work done with human tissue; most of it is with mouse models that can only get parts of the disease. Interesting to check out: the inflammasome: https://en.m.wikipedia.org/wiki/Inflammasome https://en.m.wikipedia.org/wiki/Inflammasome.
- smoyer 10y ago
  Plus it's hard to take the researcher seriously when it looks like they created their own university. "Professor Resia Pretorius of the University of Pretoria"
  - adrianN 10y ago
    > Pretoria: Capital of South Africa founding a city to start your own University sixty years later to publish a paper another hundred years later, that's what I call the long-con.
    - fasteo 10y ago
      LOL
- reasonattlm 10y ago
  You almost certainly have CMV, and that definitely contributes to the progression towards dementias via chronic inflammation and other immune dysregulation. There are many papers on CMV and immune aging if you care to go digging. Alzheimer's is as inflammation-driven as, say, heart disease. Which is to say that inflammation is a meaningful contributing factor along with all the other meaningful contributing factors. This is primarily these conditions are linked with obesity, because visceral fat is a major source of inflammation. E.g.: http://www.southampton.ac.uk/news/2016/01/blocking-brain-inflammation.page http://www.southampton.ac.uk/news/2016/01/blocking-brain-inf... http://www.manchester.ac.uk/discover/news/treatment-option-for-alzheimers-disease-possible/ http://www.manchester.ac.uk/discover/news/treatment-option-f...
pcrh 10y ago
The problem really lies with the fact that within the more than 100,000 published studies on Alzheimer's disease you are bound to find a random association between this disease and many other things. This is especially true for observational studies in people, and also true for low-powered studies in experimental animals. Experimental science, however, demands that one establishes a cause and effect relationship. There is no known cure of Alzheimer's disease, so one cannot refer to experimental medicine for an answer, with the exception of inherited dominant genetic mutations that impact only a small number of people. Unfortunately, of these mutations, those affecting the APP gene do not cause neuronal loss in mice; so the mouse models are inherently problematic. This editorial calls for a clinical trial for antimicrobials in this disease. While I doubt that Alzheimer's is caused by infectious agents, there really is no harm in trying (except perhaps to the pockets of the trial's sponsors). In fact a trial of the antibiotic minocycline was completed in 2014 [1], however the results do not appear to have been reported. [1] https://clinicaltrials.gov/ct2/show/NCT01463384 https://clinicaltrials.gov/ct2/show/NCT01463384
- sc4th1s 10y ago
  There is a cure for the mouse model of Alzheimers: http://www.fusfoundation.org/news/1535-new-pre-clinical-research-further-validates-potential-for-focused-ultrasound-in-alzheimer-s http://www.fusfoundation.org/news/1535-new-pre-clinical-rese...
- davak 10y ago
  Often negative results are never published. Great post.
- randcraw 10y ago
  Yes. I think few non-medical researchers realize how limited the value of a particular correlation generally proves to be. The more you work with biomedical data, the more you appreciate the limited value of big R values when no plausible mechanism of action accompanies it. Given enough metrics, it's common to find one with perfect correspondence to a disease's biomarkers or symptoms. Lab biologists and chemists have long ago lost interest in exploring all the miraculous sure-fire yet inexplicable signals found by data scientists. The solution in this case is for the paper's authors to spend THEIR OWN grant money underwriting the clinical trials to explore their 'discovery'.
M_Grey 10y ago
If you don't understand that correlation doesn't imply causation, you should be sent back to your first year of high school and forced to try it all again.
- pmoriarty 10y ago
  What, if not correlation, does imply causation?
  - M_Grey 10y ago
    I'm sorry, is that an incredibly lazy way of arguing that correlation does imply causation, but you feel like reversing it and dumping the burden of proof onto me? No.
    - pcrh 10y ago
      Correlation suggests causation, but does not prove it.
      - M_Grey 10y ago
        It suggests correlation; get a big enough dataset and you'll find correlations all over the place. They don't imply a causal relationship, at all. http://imgs.xkcd.com/comics/heatmap.png http://imgs.xkcd.com/comics/heatmap.png
        pcrh 10y ago
        Indeed, correlations are not sufficient to establish cause. However... things that do cause a specific effect also tend to correlate. So correlations are a basis for hypotheses that can be experimentally tested. To wit, the hypothesis presented in the post linked to by OP can be tested by treating people with Alzheimer's disease with antimicrobial agents. Unfortunately, in what concern people (disease and dying) experiments on humans (aka clinical trials) are expensive, with uncertain returns. So the experiments that could test hypotheses concerning Alzheimer's disease in real actual people are rarely performed to the level statistically needed. Instead we get a plethora of studies in mice with "suggestive"implications for what might occur in humans. Along with random studies that are not worth more than anecdotes (see those I commented on above).
eth0up 10y ago
It's interesting that viral/bacterial/fungal infections may be attributed to Alzheimer's - although undemocratically so, I still suspect prions as a culprit. Below is a link to a lecture by Professor James Ironside, University of Edinburgh, on the subject of prions. Whether such suspicions are valid or not, prions are very easy to be fascinated by, and it's a great lecture, IMO: https://www.youtube.com/watch?v=nlIYGYA5q0s https://www.youtube.com/watch?v=nlIYGYA5q0s
1_over_n 10y ago
slightly off topic but i remember a study from 2010 where it was found beetroots could help with older adults brain health the sample size was not huge (14 i think) and it was cited nitrates are the beneficial agent. It would be interesting to see if there is any association between the suggested offending microbial activity and nitrates in vitro before moving on to some sort of in vivo model https://www.sciencedaily.com/releases/2010/11/101102130957.htm https://www.sciencedaily.com/releases/2010/11/101102130957.h...
- grok2 10y ago
  Your reference to nitrates reminded me of this other topic that was on hacker news today about migraines being caused by microbes in the mouth interacting with foods containing nitrates....https://news.ycombinator.com/item?id=12747773 https://news.ycombinator.com/item?id=12747773
inputcoffee 10y ago
I read, with great hope, every Alzheimer's breakthrough but in the last year alone the key has been found out to be: 1. Exercise for oxygen 2. Gum disease 3. Standing up and feeling a head rush 4. blood sugar and diabetes If we can believe each of these 4 is the key insight within 12 months, I have to wonder at the state of our knowledge about the disease.
- 2bitencryption 10y ago
  I've read that we aren't even 100% sure that the beta-amaloyde (spelling?) plaque, which is so associated with the disease, might not even be a cause but just a side effect (or even a protecting agent in defense of the disease).

149 points by musha68k 10y ago

From the abstract towards the bottom of the page: > We refer to the many studies, mainly on humans, implicating specific microbes in the elderly brain, notably herpes simplex virus type 1 (HSV1), Chlamydia pneumoniae, and several types of spirochaete, in the etiology of AD.

jonny_eh 10y ago

This is from March. Any critiques published?

cpncrunch 10y ago
https://www.washingtonpost.com/news/speaking-of-science/wp/2016/03/14/calm-down-herpes-probably-isnt-going-to-give-you-alzheimers/ https://www.washingtonpost.com/news/speaking-of-science/wp/2...

MrQuincle 10y ago

You probably have herpes but that's okay: https://www.washingtonpost.com/news/speaking-of-science/wp/2016/03/14/calm-down-herpes-probably-isnt-going-to-give-you-alzheimers/ https://www.washingtonpost.com/news/speaking-of-science/wp/2... My wife studies Alzheimer's and I hope she will respond here, but I'm afraid she gets too angry by sensationalist stories based on editorials rather than mainline research. Of course there is inflammation involved. From what I understand talking with her, there is not much mechanistic work done with human tissue; most of it is with mouse models that can only get parts of the disease. Interesting to check out: the inflammasome: https://en.m.wikipedia.org/wiki/Inflammasome https://en.m.wikipedia.org/wiki/Inflammasome.

smoyer 10y ago
Plus it's hard to take the researcher seriously when it looks like they created their own university. "Professor Resia Pretorius of the University of Pretoria"
- adrianN 10y ago
  > Pretoria: Capital of South Africa founding a city to start your own University sixty years later to publish a paper another hundred years later, that's what I call the long-con.
  - fasteo 10y ago
    LOL
reasonattlm 10y ago
You almost certainly have CMV, and that definitely contributes to the progression towards dementias via chronic inflammation and other immune dysregulation. There are many papers on CMV and immune aging if you care to go digging. Alzheimer's is as inflammation-driven as, say, heart disease. Which is to say that inflammation is a meaningful contributing factor along with all the other meaningful contributing factors. This is primarily these conditions are linked with obesity, because visceral fat is a major source of inflammation. E.g.: http://www.southampton.ac.uk/news/2016/01/blocking-brain-inflammation.page http://www.southampton.ac.uk/news/2016/01/blocking-brain-inf... http://www.manchester.ac.uk/discover/news/treatment-option-for-alzheimers-disease-possible/ http://www.manchester.ac.uk/discover/news/treatment-option-f...

pcrh 10y ago

The problem really lies with the fact that within the more than 100,000 published studies on Alzheimer's disease you are bound to find a random association between this disease and many other things. This is especially true for observational studies in people, and also true for low-powered studies in experimental animals. Experimental science, however, demands that one establishes a cause and effect relationship. There is no known cure of Alzheimer's disease, so one cannot refer to experimental medicine for an answer, with the exception of inherited dominant genetic mutations that impact only a small number of people. Unfortunately, of these mutations, those affecting the APP gene do not cause neuronal loss in mice; so the mouse models are inherently problematic. This editorial calls for a clinical trial for antimicrobials in this disease. While I doubt that Alzheimer's is caused by infectious agents, there really is no harm in trying (except perhaps to the pockets of the trial's sponsors). In fact a trial of the antibiotic minocycline was completed in 2014 [1], however the results do not appear to have been reported. [1] https://clinicaltrials.gov/ct2/show/NCT01463384 https://clinicaltrials.gov/ct2/show/NCT01463384

sc4th1s 10y ago
There is a cure for the mouse model of Alzheimers: http://www.fusfoundation.org/news/1535-new-pre-clinical-research-further-validates-potential-for-focused-ultrasound-in-alzheimer-s http://www.fusfoundation.org/news/1535-new-pre-clinical-rese...
davak 10y ago
Often negative results are never published. Great post.
randcraw 10y ago
Yes. I think few non-medical researchers realize how limited the value of a particular correlation generally proves to be. The more you work with biomedical data, the more you appreciate the limited value of big R values when no plausible mechanism of action accompanies it. Given enough metrics, it's common to find one with perfect correspondence to a disease's biomarkers or symptoms. Lab biologists and chemists have long ago lost interest in exploring all the miraculous sure-fire yet inexplicable signals found by data scientists. The solution in this case is for the paper's authors to spend THEIR OWN grant money underwriting the clinical trials to explore their 'discovery'.

M_Grey 10y ago

If you don't understand that correlation doesn't imply causation, you should be sent back to your first year of high school and forced to try it all again.

pmoriarty 10y ago
What, if not correlation, does imply causation?
- M_Grey 10y ago
  I'm sorry, is that an incredibly lazy way of arguing that correlation does imply causation, but you feel like reversing it and dumping the burden of proof onto me? No.
  - pcrh 10y ago
    Correlation suggests causation, but does not prove it.
    - M_Grey 10y ago
      It suggests correlation; get a big enough dataset and you'll find correlations all over the place. They don't imply a causal relationship, at all. http://imgs.xkcd.com/comics/heatmap.png http://imgs.xkcd.com/comics/heatmap.png
      - pcrh 10y ago
        Indeed, correlations are not sufficient to establish cause. However... things that do cause a specific effect also tend to correlate. So correlations are a basis for hypotheses that can be experimentally tested. To wit, the hypothesis presented in the post linked to by OP can be tested by treating people with Alzheimer's disease with antimicrobial agents. Unfortunately, in what concern people (disease and dying) experiments on humans (aka clinical trials) are expensive, with uncertain returns. So the experiments that could test hypotheses concerning Alzheimer's disease in real actual people are rarely performed to the level statistically needed. Instead we get a plethora of studies in mice with "suggestive"implications for what might occur in humans. Along with random studies that are not worth more than anecdotes (see those I commented on above).

eth0up 10y ago

It's interesting that viral/bacterial/fungal infections may be attributed to Alzheimer's - although undemocratically so, I still suspect prions as a culprit. Below is a link to a lecture by Professor James Ironside, University of Edinburgh, on the subject of prions. Whether such suspicions are valid or not, prions are very easy to be fascinated by, and it's a great lecture, IMO: https://www.youtube.com/watch?v=nlIYGYA5q0s https://www.youtube.com/watch?v=nlIYGYA5q0s

1_over_n 10y ago

slightly off topic but i remember a study from 2010 where it was found beetroots could help with older adults brain health the sample size was not huge (14 i think) and it was cited nitrates are the beneficial agent. It would be interesting to see if there is any association between the suggested offending microbial activity and nitrates in vitro before moving on to some sort of in vivo model https://www.sciencedaily.com/releases/2010/11/101102130957.htm https://www.sciencedaily.com/releases/2010/11/101102130957.h...

grok2 10y ago
Your reference to nitrates reminded me of this other topic that was on hacker news today about migraines being caused by microbes in the mouth interacting with foods containing nitrates....https://news.ycombinator.com/item?id=12747773 https://news.ycombinator.com/item?id=12747773

inputcoffee 10y ago

I read, with great hope, every Alzheimer's breakthrough but in the last year alone the key has been found out to be: 1. Exercise for oxygen 2. Gum disease 3. Standing up and feeling a head rush 4. blood sugar and diabetes If we can believe each of these 4 is the key insight within 12 months, I have to wonder at the state of our knowledge about the disease.

2bitencryption 10y ago
I've read that we aren't even 100% sure that the beta-amaloyde (spelling?) plaque, which is so associated with the disease, might not even be a cause but just a side effect (or even a protecting agent in defense of the disease).