There is a conceptual framing for this hypothesis: that beta-amyloid plaques are akin to the garbage left in the stadium after a big match. The garbage itself is not the cause or raison d'etre of the stadium and its activity, yet it is a negative and fixable side-effect of the main event. I'm sure those who support the tao-hypothesis or some of the other more fringe hypotheses would be in favor of such an explanation.
It's not simply that drugs have failed time and again for Alzheimers. It's a very hard disease to come up with a treatment for. Here are some challenges:
1) It's a hard disease to detect in the earliest stages, where preventative/slowing drugs would have the most effect. If your drug slows decline by 30% but you start using the drug after 60% of the decline has already occurred, your effect size will be much smaller.
2) The blood-brain-barrier is a strong obstacle in our anatomy that prevents the passage of many potentially useful small or large molecules from general circulation into the brain.
3) Our early-stage disease models, things from petri dishes to mice, are less effective for choosing winners in this disease in particular. Maybe due to the complexity of the human neurology, though TBH I'm not sure why this is.
4) Even if you reduce beta-amyloid or other biomarkers, if you can't slow the disease progression/symptoms, then why is your drug useful? It's much harder to provide the slowing or reduction of cognitive decline than it is to simply clean up the beta-amyloid plaques. 4) is a specific case of the general use of "biomarkers" or "surrogate endpoints" - you need to measure SOME outcome, it's hard to do for cognitive diseases, so you find something measurable and look at that, though the linkage to symptoms is not totally clear in many cases.
So all of our models are pretty artificial. And we build our rat models off of our disease assumptions, like injecting rats with beta amyloid because we assume that's the primay cause of brain dysfunction.
But it's looking more and more like that's wrong and beta amyloid is not the central player in Alzheimer's but just one of many. With Tau/insulin resistance/herpes/glial dysfunction/neuroinflammation playing important rules as well.
Several rats have been developed which manifest Alzheimer's disease with all the right symptoms: age-dependent cerebral amyloidosis that precedes tauopathy, gliosis, apoptotic loss of neurons in the cerebral cortex and hippocampus, and cognitive disturbance.
Phosphorylated Tau may also play into the herpes story quite well. It regulates microtubule stability, and herpes viruses traffic on those microtubules to hop from one nueron to the next :
and subcosmos's comment "Right on the heals of the recent publication that shows that beta-amyloid in the brain specifically wraps around HerpesViral particles in order to prevent them from spreading!" (1st comment on the above).
There seems evidence the amyloid is a body defence against viral infection, mostly herpes 6&7.
I just read in the NYT about an amyloid-clearing drug called BAN2401 that just reported results of Phase 2 trials (which test the safety and efficacy of a drug). The article starts by singing the praises of the drug, which substantially reduces amyloid scores. However, it then cautions that the drug's ability to slow down cognitive decline was small.
This supports the OP: amyloid may not be the culprit. In a phase 3 trial, the drug may not pan out.
the drug's ability to slow down cognitive decline was small but statistically significant and dose dependent. It is a huge deal. It is also interesting that the drug selectively targets protofibrils. This is interesting because A/Beta peptide is difficult to target because there is so much of it. Fibrils are difficult to target because they are insoluble. Selectively targeting protofibrils means the drug binds an accessible target and will not be titrated out by A/Beta peptide.
I've read some interesting news about how people giving people with Alzheimer given a regular dose of coconut oil, maybe due to also some findings about how this could be related to a type 3 diabetes, maybe the lack of ketones in the blood, maybe the brain needs alternative energy sources, or the fat provided by those foods provides a nutrient pathway that is currently dormant or unblocks the neuronal damage in their brain. I'm not any kind of expert, but I've been reading about people who gained some benefit / therapeutic value from doing that. Saw someone post this which was interesting, https://www.ncbi.nlm.nih.gov/pubmed/24244584 so the claim is, maybe damaged metabolism using glucose, and the body needing to switch to ketone, but if someone has a compromised metabolism, say being insulin resistant, this practically shuts down ketone distribution, it also can be found to have heart implications for the future, but if the brain switches to needing fatty acids, and insulin prevents this, it might help understand how Alzheimer progresses and gets worse over time.
On a similar vein, I've often wondered if there is a link between the rise in prescription of the statin class of cholesterol drugs and the rise of Alzheimers
As much as 'coconut oil cures Alzheimer's' sounds like quackery, there is some pretty interesting evidence towards metabolic dysfunction being a major contributor to the disease. It even got mentioned in the article.
It all sounds very interesting, and I can totally believe that it might not be amyloid plaques that are the cause. I also believe we should fund multiple lines of study. BUT, I also had this odd feeling of deja vu while reading it, and eventually I realized that it sounded like some of the early HIV-skeptics, when the HIV hypothesis had been around for years but no effective treatments had been found yet.
This is a really great article outlining the current state of research in the field. It'd be nice to pin canonical articles like this every time a disease is discussed.
Too many companies want to cure a disease with a drug. It is understandable since a drug can be patented and the company can make a profit.
Unfortunately this means that diseases that do not require a drug never get cured....
Unless you name is Dr Dale Bredesen. Dr Bredesen has a methododoly instead of a drug to reverse Alzheimer. He has published about it and reverses Alzheimer in 9 out 10 patients and is currently doing new studies with a larger number of patients.
TL;DR go to bed at 10 PM, do stress management, exercise a little, eat well and take supplements (blood tests determine which ones), and take a couple of other substances that our body needs, Alzheimer's disappears in less than 4 months.
Can you provide a link to that research? I'm somewhat connected to Alzheimers research professionally, I study dementia and delirium in the elderly. I have not heard of that and it honestly sounds impossible. If such a simple solution were on offer and so wonderful, surely blinded randomized clinical trials would bear the evidence needed to support your very strong assertions. Keep in mind over 5 million die from Alzheimers each year in the USA, and that will triple over time. It's not something to speak lightly about or spread misinformation about.
This is the most preliminary evidence possible. Just a couple of case studies. It'll be interesting to see how this pans out with larger trials but there are plenty of Alzheimer drugs that have had far more evidence for their effectiveness then this regimen, and ultimately failed to make any meaningful difference.
Yes they accept that large trials are obviously needed.
> The results suggest that memory loss may be reversed and improvement sustained with the therapeutic program, but Bredesen cautioned that the results need to be replicated.
> “The current, anecdotal results require a larger trial, not only to confirm or refute the results reported here, but also to address key questions raised, such as the degree of improvement that can be achieved routinely, how late in the course of cognitive decline reversal can be effected, whether such an approach may be effective in patients with familial Alzheimer’s disease, and last, how long improvement can be sustained,” he said.
There are no more published results. In interviews Dr Bredesen confirms that the patients after 4 years on the protocol still are without Alzheimer.
One more anecdotal story: one patient did not like the protocol and stopped, Alzheimer returned, started the protocol again, Alzheimer reversed. This happened various times with the same patient. Make your own conclusions/assumptions.
There is a new study with ~100 patients but is is not yet finished.
While sleep, exercise, healthy food, etc may certainly prevent or delay the onset [1], once you have Alzheimer's, it is too late. This is like telling someone with gangrene that all they need is neosporin, a fresh bandage, and rest. Except it is too late for that once you have gangrene, your only options are antibiotics or amputation.
Oh I get it. I have heard the same stuff about cancer, heart disease, and every other major disease. And yet the people who take the natural route end up dying sooner on average. Once a disease progresses to a certain point, diet and exercise stop working as a treatment because the disease has already done too much damage.
Is it possible that there is a natural cure for Alzheimer's? Given we don't know the cause yet, sure it is possible. But one study with 10 people is not enough evidence to claim there is one. If you simply said "hey I found this interesting, published study that suggests there may be a natural treatment", then you probably wouldn't have been down voted to hell. Instead you asserted that there is a natural treatment with very little evidence.
Anything that delays or prevents Alzheimer's is certainly interesting so why so dogmatic? Would 'evidence to date suggests that ... it is almost certainly too late' not be more in line? Your analogy comes with a large assumption.
> Too many companies want to cure a disease with a drug.
Sustained treatment of symptoms is where the money is, cures are not. Putting patients on a maintenance drug regimen is longterm revenue stream.
> He has published about it and reverses Alzheimer in 9 out 10 patients and is currently doing new studies with a larger number of patients. TL;DR go to bed at 10 PM, do stress management, exercise a little, eat well and take supplements (blood tests determine which ones), and take a couple of other substances that our body needs, Alzheimer's disappears in less than 4 months.
Interesting results, but it'd be great if someone reproduced that at a large scale.
On a similar note, you can cure type 2 diabetes in nearly any patient by putting them on a healthy diet of 800 calories a day for about 5 months, and then slowly growing their caloric intake back up to around 1500 a day (which is probably about the maximum necessary amount for most adult males in todays sedentary societal environment). This is well studied, proven, and reproducible, but telling people to not overeat and to avoid garbage food is not a particularly profitable endeavor.
> 10 PM, do stress management, exercise a little, eat well a
Most people won't do those things, but will take a pill. Also, there's no need for a whole company to invent clean living or whatever, that's mostly the purview of TEDx talks and self-help authors.
There is a conceptual framing for this hypothesis: that beta-amyloid plaques are akin to the garbage left in the stadium after a big match. The garbage itself is not the cause or raison d'etre of the stadium and its activity, yet it is a negative and fixable side-effect of the main event. I'm sure those who support the tao-hypothesis or some of the other more fringe hypotheses would be in favor of such an explanation.
It's not simply that drugs have failed time and again for Alzheimers. It's a very hard disease to come up with a treatment for. Here are some challenges:
1) It's a hard disease to detect in the earliest stages, where preventative/slowing drugs would have the most effect. If your drug slows decline by 30% but you start using the drug after 60% of the decline has already occurred, your effect size will be much smaller.
2) The blood-brain-barrier is a strong obstacle in our anatomy that prevents the passage of many potentially useful small or large molecules from general circulation into the brain.
3) Our early-stage disease models, things from petri dishes to mice, are less effective for choosing winners in this disease in particular. Maybe due to the complexity of the human neurology, though TBH I'm not sure why this is.
4) Even if you reduce beta-amyloid or other biomarkers, if you can't slow the disease progression/symptoms, then why is your drug useful? It's much harder to provide the slowing or reduction of cognitive decline than it is to simply clean up the beta-amyloid plaques. 4) is a specific case of the general use of "biomarkers" or "surrogate endpoints" - you need to measure SOME outcome, it's hard to do for cognitive diseases, so you find something measurable and look at that, though the linkage to symptoms is not totally clear in many cases.
#3 is because rats don't get Alzheimer's.
So all of our models are pretty artificial. And we build our rat models off of our disease assumptions, like injecting rats with beta amyloid because we assume that's the primay cause of brain dysfunction.
But it's looking more and more like that's wrong and beta amyloid is not the central player in Alzheimer's but just one of many. With Tau/insulin resistance/herpes/glial dysfunction/neuroinflammation playing important rules as well.
Several rats have been developed which manifest Alzheimer's disease with all the right symptoms: age-dependent cerebral amyloidosis that precedes tauopathy, gliosis, apoptotic loss of neurons in the cerebral cortex and hippocampus, and cognitive disturbance.
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496102/ [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3720142/
Phosphorylated Tau may also play into the herpes story quite well. It regulates microtubule stability, and herpes viruses traffic on those microtubules to hop from one nueron to the next :
https://medium.com/@InfinoMe/cholesterol-have-we-shot-the-me...
I thought we'd cleared this up on HN last week with 'Alzheimer's risk 10 times lower with herpes medication' https://news.ycombinator.com/item?id=17540094
and subcosmos's comment "Right on the heals of the recent publication that shows that beta-amyloid in the brain specifically wraps around HerpesViral particles in order to prevent them from spreading!" (1st comment on the above).
There seems evidence the amyloid is a body defence against viral infection, mostly herpes 6&7.
hacker news continues to push forward the state of alzheimers research one comment at a time
is herpes one instance of a general class of proteins/virus/bodies that causes amyloid alleged defense response or is it exactly because of herpes ?
I just read in the NYT about an amyloid-clearing drug called BAN2401 that just reported results of Phase 2 trials (which test the safety and efficacy of a drug). The article starts by singing the praises of the drug, which substantially reduces amyloid scores. However, it then cautions that the drug's ability to slow down cognitive decline was small.
This supports the OP: amyloid may not be the culprit. In a phase 3 trial, the drug may not pan out.
source: nyti.ms/2JWjznT
the drug's ability to slow down cognitive decline was small but statistically significant and dose dependent. It is a huge deal. It is also interesting that the drug selectively targets protofibrils. This is interesting because A/Beta peptide is difficult to target because there is so much of it. Fibrils are difficult to target because they are insoluble. Selectively targeting protofibrils means the drug binds an accessible target and will not be titrated out by A/Beta peptide.
I've read some interesting news about how people giving people with Alzheimer given a regular dose of coconut oil, maybe due to also some findings about how this could be related to a type 3 diabetes, maybe the lack of ketones in the blood, maybe the brain needs alternative energy sources, or the fat provided by those foods provides a nutrient pathway that is currently dormant or unblocks the neuronal damage in their brain. I'm not any kind of expert, but I've been reading about people who gained some benefit / therapeutic value from doing that. Saw someone post this which was interesting, https://www.ncbi.nlm.nih.gov/pubmed/24244584 so the claim is, maybe damaged metabolism using glucose, and the body needing to switch to ketone, but if someone has a compromised metabolism, say being insulin resistant, this practically shuts down ketone distribution, it also can be found to have heart implications for the future, but if the brain switches to needing fatty acids, and insulin prevents this, it might help understand how Alzheimer progresses and gets worse over time.
On a similar vein, I've often wondered if there is a link between the rise in prescription of the statin class of cholesterol drugs and the rise of Alzheimers
As much as 'coconut oil cures Alzheimer's' sounds like quackery, there is some pretty interesting evidence towards metabolic dysfunction being a major contributor to the disease. It even got mentioned in the article.
Recent and related: https://news.ycombinator.com/item?id=17444214.
Also, this submission was in response to https://news.ycombinator.com/item?id=17617054.
It all sounds very interesting, and I can totally believe that it might not be amyloid plaques that are the cause. I also believe we should fund multiple lines of study. BUT, I also had this odd feeling of deja vu while reading it, and eventually I realized that it sounded like some of the early HIV-skeptics, when the HIV hypothesis had been around for years but no effective treatments had been found yet.
This is a really great article outlining the current state of research in the field. It'd be nice to pin canonical articles like this every time a disease is discussed.
Are there any good Twitter Lists for Alzheimer's research?
Too many companies want to cure a disease with a drug. It is understandable since a drug can be patented and the company can make a profit. Unfortunately this means that diseases that do not require a drug never get cured.... Unless you name is Dr Dale Bredesen. Dr Bredesen has a methododoly instead of a drug to reverse Alzheimer. He has published about it and reverses Alzheimer in 9 out 10 patients and is currently doing new studies with a larger number of patients. TL;DR go to bed at 10 PM, do stress management, exercise a little, eat well and take supplements (blood tests determine which ones), and take a couple of other substances that our body needs, Alzheimer's disappears in less than 4 months.
Have his results been replicated? It's been 3 or 4 years since his work was published (per https://seniorplanet.org/can-a-controversial-new-treatment-r...).
Sorry, not yet. There is a new study going on with ~100 patients and the only comment that was made is "the results are similar to the first one".
Can you provide a link to that research? I'm somewhat connected to Alzheimers research professionally, I study dementia and delirium in the elderly. I have not heard of that and it honestly sounds impossible. If such a simple solution were on offer and so wonderful, surely blinded randomized clinical trials would bear the evidence needed to support your very strong assertions. Keep in mind over 5 million die from Alzheimers each year in the USA, and that will triple over time. It's not something to speak lightly about or spread misinformation about.
This is likely the study referred to, out of UCLA:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221920/
This is the most preliminary evidence possible. Just a couple of case studies. It'll be interesting to see how this pans out with larger trials but there are plenty of Alzheimer drugs that have had far more evidence for their effectiveness then this regimen, and ultimately failed to make any meaningful difference.
Yes they accept that large trials are obviously needed.
> The results suggest that memory loss may be reversed and improvement sustained with the therapeutic program, but Bredesen cautioned that the results need to be replicated.
> “The current, anecdotal results require a larger trial, not only to confirm or refute the results reported here, but also to address key questions raised, such as the degree of improvement that can be achieved routinely, how late in the course of cognitive decline reversal can be effected, whether such an approach may be effective in patients with familial Alzheimer’s disease, and last, how long improvement can be sustained,” he said.
From http://newsroom.ucla.edu/releases/memory-loss-associated-wit...
There are no more published results. In interviews Dr Bredesen confirms that the patients after 4 years on the protocol still are without Alzheimer. One more anecdotal story: one patient did not like the protocol and stopped, Alzheimer returned, started the protocol again, Alzheimer reversed. This happened various times with the same patient. Make your own conclusions/assumptions.
There is a new study with ~100 patients but is is not yet finished.
When that is published, please post it to HN!
Yesterday news came out that AHNP Precision Health, which bought the lab of Dr Bredesen, is now using the protocol to treat patients: https://markets.businessinsider.com/news/stocks/ahnp-precisi... AHNP Precision Health is here: https://www.ahnphealth.com/
That’s really interesting. Do you have a link?
While sleep, exercise, healthy food, etc may certainly prevent or delay the onset [1], once you have Alzheimer's, it is too late. This is like telling someone with gangrene that all they need is neosporin, a fresh bandage, and rest. Except it is too late for that once you have gangrene, your only options are antibiotics or amputation.
1. https://www.ted.com/talks/lisa_genova_what_you_can_do_to_pre...
you did not get it. Dr Bredesen does reverse Alzheimer in 9 out of 10 patients. No theory or BS here.
Oh I get it. I have heard the same stuff about cancer, heart disease, and every other major disease. And yet the people who take the natural route end up dying sooner on average. Once a disease progresses to a certain point, diet and exercise stop working as a treatment because the disease has already done too much damage.
Is it possible that there is a natural cure for Alzheimer's? Given we don't know the cause yet, sure it is possible. But one study with 10 people is not enough evidence to claim there is one. If you simply said "hey I found this interesting, published study that suggests there may be a natural treatment", then you probably wouldn't have been down voted to hell. Instead you asserted that there is a natural treatment with very little evidence.
ok, you do want to get it. This doctor publishes data about 10 patients that are made up.
The study was not a double-blind, placebo trial which means the positive result could have been because one of the following:
1. Patients didn't actually have Alzheimer's. Given the only definitive test for it is a brain exam after death, this is possible.
2. There was a placebo effect.
3. There was a therapeutic effect better than placebo.
You are assuming #3 but we can't draw that conclusion yet. Even the authors of the study aren't claiming #3.
https://markets.businessinsider.com/news/stocks/ahnp-precisi...
What does that prove?
Did he try it on those patients alone? Or did he pick the ones that for some reason supported his findings?
Would you call such a small sample as relevant?
Ah yes, the "Steve Jobs" cure. Just take better care of yourself and you can cure cancer/hiv/Alzheimers without any drugs.
Your entire submission history appears to be almost solely PR releases from/regarding Dr Bredesen and his claimed Alzheimer cure.[1]
May I ask what your interest in this is? Is there any relationship you should disclose?
[1] https://news.ycombinator.com/submitted?id=mhkool
Anything that delays or prevents Alzheimer's is certainly interesting so why so dogmatic? Would 'evidence to date suggests that ... it is almost certainly too late' not be more in line? Your analogy comes with a large assumption.
> Too many companies want to cure a disease with a drug.
Sustained treatment of symptoms is where the money is, cures are not. Putting patients on a maintenance drug regimen is longterm revenue stream.
> He has published about it and reverses Alzheimer in 9 out 10 patients and is currently doing new studies with a larger number of patients. TL;DR go to bed at 10 PM, do stress management, exercise a little, eat well and take supplements (blood tests determine which ones), and take a couple of other substances that our body needs, Alzheimer's disappears in less than 4 months.
Here is the study you reference, out of UCLA:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221920/
Interesting results, but it'd be great if someone reproduced that at a large scale.
On a similar note, you can cure type 2 diabetes in nearly any patient by putting them on a healthy diet of 800 calories a day for about 5 months, and then slowly growing their caloric intake back up to around 1500 a day (which is probably about the maximum necessary amount for most adult males in todays sedentary societal environment). This is well studied, proven, and reproducible, but telling people to not overeat and to avoid garbage food is not a particularly profitable endeavor.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6...
> 10 PM, do stress management, exercise a little, eat well a
Most people won't do those things, but will take a pill. Also, there's no need for a whole company to invent clean living or whatever, that's mostly the purview of TEDx talks and self-help authors.
BUT if you do the whole package, Alzheimer goes away. I suggest to read https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221920/
wow! step back and read what you wrote. it sounds like the writings of a total crank.
Please don't be uncivil or call names in arguments, regardless of how wrong you think someone is.
https://news.ycombinator.com/newsguidelines.html