Salicylate For Alzheimers (Aspirin)

haidut

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ken said:

Thanks for that study. I am waiting to get a copy from the authors but it looks like it is very promising. Here is a quote from another news source.

http://www.eurekalert.org/pub_releases/ ... 091715.php

"..."We identified for the first time a pharmacological approach that reverses all aspects of tau toxicity," says co-senior author Li Gan, PhD, an associate investigator at the Gladstone Institutes. "Remarkably, the profound protective effects of salsalate were achieved even though it was administered after disease onset, indicating that it may be an effective treatment option." Although tau has been a target in dementia research for some time, there are no tau-targeted drugs available for patients. Additionally, how the protein builds up in the brain, causing toxicity and contributing to disease, still remains largely a mystery. "

And here is a link to the actual study:
http://www.nature.com/nm/journal/vaop/n ... .3951.html
 
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haidut

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OK, I just got a copy of the study from the authors. It is pretty impressive, especially the fact that salicylate was able to fully reverse established tau pathology in the best known animal model for Alzheimers.
The human equivalent dose used in the study was 16mg/kg, or as the paper states:
"...Notably, the dosage (225 mg/kg) used in our study is equivalent to ~1,350 mg per day for a 75-kg person[49], lower than the dose typically prescribed (3,000 mg per day). Our study supports clinical evaluation of SSA and its derivatives as therapies in human tauopathies."

Given that salsalate was used as a prodrug for salicylate and it was salicylate that had the beneficial effect, ingesting aspirin should provide equivalent results. The dose of aspirin required to achieve the same salicylate concentrations as salsalate is 30% more than the respective dose of salsalate. So, the 1,350mg salsalate used in the study would be equivalent to 1,750mg aspirin to achieve the same concentrations of salicylic acid. Btw, the study itself says that people taking aspirin (for other reasons and at a low dose) already have much lower risk of getting Alzheimers.
 

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:yeahthat :1
 
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I think they tried aspirin and the acetic acid part caused it to fail.
 
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They tried aspirin."Pharmacokinetically, SSA is quickly metabolized into its active component, salicylate. Unlike salicylate, aspirin (acetylsalicylate) leads to higher levels of ac-tau in cultured neurons. SSA and aspirin have been widely used to treat rheumatoid arthritis and related illnesses in the past decades, and work presumably via inhibition of cyclo-oxygenase (COX). Interestingly, patients taking NSAIDs, including salicylate and derivatives, have a reduced risk of AD."
 

haidut

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ken said:
post 100881 They tried aspirin."Pharmacokinetically, SSA is quickly metabolized into its active component, salicylate. Unlike salicylate, aspirin (acetylsalicylate) leads to higher levels of ac-tau in cultured neurons. SSA and aspirin have been widely used to treat rheumatoid arthritis and related illnesses in the past decades, and work presumably via inhibition of cyclo-oxygenase (COX). Interestingly, patients taking NSAIDs, including salicylate and derivatives, have a reduced risk of AD."

Yes, I saw that and I sent them an urgent email. They should know better that aspirin has a very short half-life of about 10 - 15 minutes only and then quickly breaks into acetic acid and salicylic acid. So, IN VITRO you may be able to expose neurons to aspirin but IN VIVO it is impossible unless you inject it directly into the brain. So, IN VIVO, aspirin will have the same pharmacokinetic profile as salsalate and the same benefit. Both salsalate and aspirin are listed as prodrugs for salicylic acid in vivo, so that should have been a reason enough to consider it for the study.
I am actually quite ticked off at the scientists for not trying aspirin as one of the test groups. This could have been a blockbuster study and a news item with the title "Aspirin cures Alzheimers". Let's see what they respond with...
 
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Giraffe

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What does this mean practically? Do they hope to prevent/slow down further decline? Or is there any chance that patients suffering from Alzheimer's recover?
 

haidut

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Giraffe said:
post 100947 "We identified for the first time a pharmacological approach that reverses all aspects of tau toxicity," says co-senior author Li Gan, PhD, an associate investigator at the Gladstone Institutes. "Remarkably, the profound protective effects of salsalate were achieved even though it was administered after disease onset, indicating that it may be an effective treatment option." Although tau has been a target in dementia research for some time, there are no tau-targeted drugs available for pati

Did you see my post above with the quote from the study? I think it is pretty clear in what it says - i.e. salicylic acid can reverse all aspects of Alzheimer and works even when the disease is already well established.
 
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Giraffe

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haidut said:
post 100954 Did you see my post above with the quote from the study? I think it is pretty clear in what it says - i.e. salicylic acid can reverse all aspects of Alzheimer and works even when the disease is already well established.
Thanks for the clarification. I read it, but I did not understand it. I don't know what "tau pathology" is.

Three aspirin (500 mg each) is the dose for a 60 kg person (female, 75 years, advanced Alzheimer's disease)?
 
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haidut

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Giraffe said:
post 100957
haidut said:
post 100954 Did you see my post above with the quote from the study? I think it is pretty clear in what it says - i.e. salicylic acid can reverse all aspects of Alzheimer and works even when the disease is already well established.
Thanks for the clarification. I read it, but I did not understand it. I don't know what "tau pathology" is.

Three aspirin (500 mg each) is the dose for a 60 kg person (female, 75 years, advanced Alzheimer's disease)?

Tau pathology is what they call Alzheimers in scientific circles. Yes, a total daily dose of 1,500mg aspirin sounds about right. I would take some vitamin K2 with is possible as it synergizes with aspirin effects on the brain.
 
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narouz

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I think my mind couldn't process this for a while.
Sounds too good to be true. :)
 
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When I read the aspirin mention I imagined that the acetyl part of aspirin was the problem. Possibly acetyling the tau protein. Just an uninformed guess.
 
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Also the salsalate seemed a whole order of magnitude more expensive on the internet. Maybe they want to make a legacy drug out of it.
 

haidut

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ken said:
post 101186 Also the salsalate seemed a whole order of magnitude more expensive on the internet. Maybe they want to make a legacy drug out of it.

That is my guess. The scientists have gone silent over my email about aspirin and how in IN VIVO it is indistinguishable from salsalate. I will keep bugging them but it is pretty clear that they don't want to answer.
 
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haidut said:
post 101216
ken said:
post 101186 Also the salsalate seemed a whole order of magnitude more expensive on the internet. Maybe they want to make a legacy drug out of it.

That is my guess. The scientists have gone silent over my email about aspirin and how in IN VIVO it is indistinguishable from salsalate. I will keep bugging them but it is pretty clear that they don't want to answer.

:ss
 
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haidut

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Good news people! After some back and forth between me and the authors who asked that I identify myself, I just got this email from them.

"...You have a point about the in vivo metabolism of aspirin. We didn't test aspirin due to the lack of in vitro efficacy. It does not mean it wouldn't work. I think a large part of the experimental design would depend on your rodent model. Our study pointed to the effects on tau-mediated toxicity; not sure how it would affect toxicity caused by other tau-independent mechanisms. I would be interested o know your results, whenever you're ready to share."

So, I think you can spread the word far and wide - aspirin cures Alzheimer disease (AD)! Now, what would happen if we combine aspirin and methylene blue...
Something so simple yet so effective against virtually any disease. To keep things in perspective I will just point out this thread.
viewtopic.php?f=10&t=4229

Billions upon billions of wasted money, a good chunk of which is taxpayer money, when something so simple and so effective is available for pennies...
 
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haidut said:
post 101301
So, I think you can spread the word far and wide - aspirin cures Alzheimer disease (AD)!

Shhh :yipes

giphy.gif
 
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