5 ms·

Former Alzheimer's researcher here. I've never heard of this before. Some cursory googling only turns up a sole author publication by Alan MacDonald in Medical

Former Alzheimer's researcher here. I've never heard of this before. Some cursory googling only turns up a sole author publication by Alan MacDonald in Medical Hypotheses and a few news pieces by dodgy organizations like the Spirochaetal Alzheimer's Assocation. Despite what a lot of people learn in undergrad psych classes, the evidence linking amyloid beta and tau to AD is quite good and getting stronger with every new molecular paper that comes out. BTW, there doesn't seem to be a correlation between Lyme disease incidence and AD https://www.ncbi.nlm.nih.gov/pubmed/24840565 https://www.ncbi.nlm.nih.gov/pubmed/24840565

Danihan 9y ago
> the evidence linking amyloid beta and tau to AD is quite good and getting stronger with every new molecular paper that comes out. Sure, but what causes the amyloid beta? Why wouldn't a long-standing syphilis-like bacterial infection in the CNS cause that sort of protein buildup? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4399390/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4399390/ It's a little shocking to see a "former Alzeheimer's researcher" presume that tau buildup and bacterial infections are mutually exclusive.. That's like saying heart disease can't be caused by arterial scarring because it's caused by plaque buildup.
- Nomentatus 9y ago
  I.e. "But dudes, just WHY is the garbage piling up faster than it can be cleared, now?" Love your plaque line - although plaque is compensation and amyloid beta and tau are not, or not per se.
  - Danihan 9y ago
    Not per se, correct. The plaques seem almost similar to remnants of an incomplete chemical synthesis. For instance, glutamate is synthesized in the brain and is used as a neurotransmitter. If a bacterial infection prevented glutamate synthesization (potentially by utilizing some crucial component for it's own propagation), you'd see a build-up of otherwise useful amino acids that would manifest as plaques. The plaques should hypothetically be cleaned by neuronal autophagy but something could be throwing that off as well. And if neurotransmitter production is degraded, of course cognition will suffer. You seem similar symptoms in Schizophrenia as well.
    - Nomentatus 9y ago
      Below I am reinterpreting your first sentence as "Not 'per se', correct." (Your original has roughly the opposite meaning of this interpretation, but I've been known to omit metaspeech-indicating quotation marks, myself.) Your answer is interesting. For those following I should note that compensation means a curative or attempted curative event (as opposed to a disease event such as bacterial infection.) As what is probably an aside, neurotransmitter production being actively downregulated as a compensatory mechanism (to lower local metabolism needs) is possible, and an interesting thought (whether my thought or your thought) (just not one that creates a buildup of tau etc.) I haven't encountered any evidence that this is compensatory and not just a downstream effect. Your mileage may vary. The evidence that mental activity reduces disease progression might be taken as disconfirmation of such an hypothesis - except that mental practice could be helping mask the underlying (progress of the) disease by increasing skill/adaptation. Re schizophrenia, I now think of it as a definition affected by a kind of "publication bias." The underlying disease process (or processes) may have rather random results depending on just what part of the brain is most affected - only when the amygdala is strongly affected is a patient likely to get a diagnosis of Schizophrenia, since this can make them (or make them seem) "a danger of self or others."
- Mz 9y ago
  Sure, but what causes the amyloid beta? Recent research shows that lack of sleep increases both amyloid beta and tau. One of them increases after a single bad night. The other takes a few days of too little sleep to start spiking. There may be other factors, but the research suggests we need to work on sleep hygiene for at risk populations. This is a non drug intervention that I can wholly get behind.
  - trendia 9y ago
    I found a study to back this up [0] > "Spinal taps showed that the more deep sleep people missed out on, the higher their levels of A-beta in the morning. Tau levels didn’t budge because of just one night of slow-wave sleep disruption, but people whose activity monitors indicated they had slept poorly the week before the test also had higher levels of that protein." https://www.sciencenews.org/article/just-one-night-poor-sleep-can-boost-alzheimers-beta-proteins https://www.sciencenews.org/article/just-one-night-poor-slee...
cing 9y ago
> "evidence linking amyloid beta and tau to AD is quite good" About 100 discontinued clinical trials targeting amyloid beta disagree with you there, https://www.nature.com/articles/nrd.2017.194 https://www.nature.com/articles/nrd.2017.194
- kurthr 9y ago
  Correlation need not be causation, but does imply linkage.
reasonattlm 9y ago
There is a fair amount of more recent research in support of a microbial contribution to Alzheimers, and rather than just mediating through inflammation, disrupting metabolism in ways that accelerate amyloid deposition. I believe this ties more closely with research into vascular amyloid, if you look at who is involved, which may be why you haven't encountered it. You might see https://doi.org/10.3389/fnagi.2017.00336 https://doi.org/10.3389/fnagi.2017.00336 as a sample review paper that talks about oral bacteria that are capable of spurring amyloid formation in addition to spirochetes. Lastly one of the complaints I've heard from someone involved in the cerebrospinal fluid drainage side of Alzheimer's research is that it is really, really hard to fight the amyloid clearance by immunotherapy dominant faction to get any funding or attention for alternatives. They just don't want to hear it.
vimy 9y ago
Maybe there is no correlation because Lyme disease is severely underreported. A couple years ago, the CDC stated that official numbers were likely underreported by a factor of 10. From 30,000 yearly cases to 300,000 https://www.cdc.gov/media/releases/2013/p0819-lyme-disease.html https://www.cdc.gov/media/releases/2013/p0819-lyme-disease.h... There was also the case of actor/songwriter Kris Kristofferson being misdiagnosed with Alzheimer's for years. He had Lyme. This is anecdotal of course. https://www.cbsnews.com/news/kris-kristofferson-misdiagnosed-alzheimers-has-lyme-disease/ https://www.cbsnews.com/news/kris-kristofferson-misdiagnosed...
- busterarm 9y ago
  The worry for me is the way this thread plays out is pretty much the textbook case for how pharmaceuticals manufacture demand for a drug. 1) Develop a drug (or find one to remarket). Find a disease that it treats or invent one. 2) Pump money into advocacy groups devoted to the disease. 3) Find research that supports the use of your drug. 4) The advocacy group spreads awareness of the disease, even if it's made up, and people start asking their doctors to test for it. Some may even receive a diagnosis. 5) Public pressure reaches the FDA, AMA, et al to consider the use of the drug for treatment.
  - paulajohnson 9y ago
    3a) If research doesn't exist, find some impecunious person with a PhD and pay them to create some.
- bo1024 9y ago
  Under-reporting of Lyme actually shouldn't impact a finding of no link as as far as I can tell. Despite the under-reporting, we still know where Lyme is more or less prevalent in the US, and I believe there will be very big differences due to climate and where ticks who carry Lyme tend to live. If prevalence of Alzheimers doesn't correlate with those big differences, that seems pretty clear. (edit) Thinking about it more, I think the anecdote you mentioned is a bit different from the parent posts. The anecdote is about a misdiagnosis (he only had Lyme, not Alzheimers), while the parent posts are about people actually having both diseases.

Danihan 9y ago

> the evidence linking amyloid beta and tau to AD is quite good and getting stronger with every new molecular paper that comes out. Sure, but what causes the amyloid beta? Why wouldn't a long-standing syphilis-like bacterial infection in the CNS cause that sort of protein buildup? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4399390/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4399390/ It's a little shocking to see a "former Alzeheimer's researcher" presume that tau buildup and bacterial infections are mutually exclusive.. That's like saying heart disease can't be caused by arterial scarring because it's caused by plaque buildup.

Nomentatus 9y ago
I.e. "But dudes, just WHY is the garbage piling up faster than it can be cleared, now?" Love your plaque line - although plaque is compensation and amyloid beta and tau are not, or not per se.
- Danihan 9y ago
  Not per se, correct. The plaques seem almost similar to remnants of an incomplete chemical synthesis. For instance, glutamate is synthesized in the brain and is used as a neurotransmitter. If a bacterial infection prevented glutamate synthesization (potentially by utilizing some crucial component for it's own propagation), you'd see a build-up of otherwise useful amino acids that would manifest as plaques. The plaques should hypothetically be cleaned by neuronal autophagy but something could be throwing that off as well. And if neurotransmitter production is degraded, of course cognition will suffer. You seem similar symptoms in Schizophrenia as well.
  - Nomentatus 9y ago
    Below I am reinterpreting your first sentence as "Not 'per se', correct." (Your original has roughly the opposite meaning of this interpretation, but I've been known to omit metaspeech-indicating quotation marks, myself.) Your answer is interesting. For those following I should note that compensation means a curative or attempted curative event (as opposed to a disease event such as bacterial infection.) As what is probably an aside, neurotransmitter production being actively downregulated as a compensatory mechanism (to lower local metabolism needs) is possible, and an interesting thought (whether my thought or your thought) (just not one that creates a buildup of tau etc.) I haven't encountered any evidence that this is compensatory and not just a downstream effect. Your mileage may vary. The evidence that mental activity reduces disease progression might be taken as disconfirmation of such an hypothesis - except that mental practice could be helping mask the underlying (progress of the) disease by increasing skill/adaptation. Re schizophrenia, I now think of it as a definition affected by a kind of "publication bias." The underlying disease process (or processes) may have rather random results depending on just what part of the brain is most affected - only when the amygdala is strongly affected is a patient likely to get a diagnosis of Schizophrenia, since this can make them (or make them seem) "a danger of self or others."
Mz 9y ago
Sure, but what causes the amyloid beta? Recent research shows that lack of sleep increases both amyloid beta and tau. One of them increases after a single bad night. The other takes a few days of too little sleep to start spiking. There may be other factors, but the research suggests we need to work on sleep hygiene for at risk populations. This is a non drug intervention that I can wholly get behind.
- trendia 9y ago
  I found a study to back this up [0] > "Spinal taps showed that the more deep sleep people missed out on, the higher their levels of A-beta in the morning. Tau levels didn’t budge because of just one night of slow-wave sleep disruption, but people whose activity monitors indicated they had slept poorly the week before the test also had higher levels of that protein." https://www.sciencenews.org/article/just-one-night-poor-sleep-can-boost-alzheimers-beta-proteins https://www.sciencenews.org/article/just-one-night-poor-slee...

cing 9y ago

> "evidence linking amyloid beta and tau to AD is quite good" About 100 discontinued clinical trials targeting amyloid beta disagree with you there, https://www.nature.com/articles/nrd.2017.194 https://www.nature.com/articles/nrd.2017.194

kurthr 9y ago
Correlation need not be causation, but does imply linkage.

reasonattlm 9y ago

There is a fair amount of more recent research in support of a microbial contribution to Alzheimers, and rather than just mediating through inflammation, disrupting metabolism in ways that accelerate amyloid deposition. I believe this ties more closely with research into vascular amyloid, if you look at who is involved, which may be why you haven't encountered it. You might see https://doi.org/10.3389/fnagi.2017.00336 https://doi.org/10.3389/fnagi.2017.00336 as a sample review paper that talks about oral bacteria that are capable of spurring amyloid formation in addition to spirochetes. Lastly one of the complaints I've heard from someone involved in the cerebrospinal fluid drainage side of Alzheimer's research is that it is really, really hard to fight the amyloid clearance by immunotherapy dominant faction to get any funding or attention for alternatives. They just don't want to hear it.

vimy 9y ago

Maybe there is no correlation because Lyme disease is severely underreported. A couple years ago, the CDC stated that official numbers were likely underreported by a factor of 10. From 30,000 yearly cases to 300,000 https://www.cdc.gov/media/releases/2013/p0819-lyme-disease.html https://www.cdc.gov/media/releases/2013/p0819-lyme-disease.h... There was also the case of actor/songwriter Kris Kristofferson being misdiagnosed with Alzheimer's for years. He had Lyme. This is anecdotal of course. https://www.cbsnews.com/news/kris-kristofferson-misdiagnosed-alzheimers-has-lyme-disease/ https://www.cbsnews.com/news/kris-kristofferson-misdiagnosed...

busterarm 9y ago
The worry for me is the way this thread plays out is pretty much the textbook case for how pharmaceuticals manufacture demand for a drug. 1) Develop a drug (or find one to remarket). Find a disease that it treats or invent one. 2) Pump money into advocacy groups devoted to the disease. 3) Find research that supports the use of your drug. 4) The advocacy group spreads awareness of the disease, even if it's made up, and people start asking their doctors to test for it. Some may even receive a diagnosis. 5) Public pressure reaches the FDA, AMA, et al to consider the use of the drug for treatment.
- paulajohnson 9y ago
  3a) If research doesn't exist, find some impecunious person with a PhD and pay them to create some.
bo1024 9y ago
Under-reporting of Lyme actually shouldn't impact a finding of no link as as far as I can tell. Despite the under-reporting, we still know where Lyme is more or less prevalent in the US, and I believe there will be very big differences due to climate and where ticks who carry Lyme tend to live. If prevalence of Alzheimers doesn't correlate with those big differences, that seems pretty clear. (edit) Thinking about it more, I think the anecdote you mentioned is a bit different from the parent posts. The anecdote is about a misdiagnosis (he only had Lyme, not Alzheimers), while the parent posts are about people actually having both diseases.