Bumetanide for APOE4 Carriers

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antimatter37
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Bumetanide for APOE4 Carriers

Post by antimatter37 »

Interesting article in "Nature Aging". In this research done by the Gladstone Institute, bumetanide, a common diuretic was found to reduce the instance of AD in APOE4 carriers.

"A commonly available oral diuretic pill approved by the U.S. Food and Drug Administration may be a potential candidate for an Alzheimer’s disease treatment for those who are at genetic risk, according to findings published in Nature Aging. The research included analysis showing that those who took bumetanide — a commonly used and potent diuretic(link is external) — had a significantly lower prevalence of Alzheimer’s disease compared to those not taking the drug."

"Researchers found that treating mice which expressed the human APOE4 gene reduced learning and memory deficits. The neutralizing effects were also confirmed in the human cell-based models, which led to the hypothesis that people already taking bumetanide should have lower rates of Alzheimer’s. To test this, the team pared down electronic health record data sets from more than 5 million people to two groups: adults over 65 who took bumetanide and a matching group who did not take bumetanide. The analysis showed that those who had the genetic risk and took bumetanide had a ~35% to 75% lower prevalence of Alzheimer’s disease compared to those not taking the drug."

The above is from a review on NIH.Gov:

https://www.nih.gov/news-events/news-re ... -treatment

Kind of an amazing result in some ways if it can be verified. One wonders how this diuretic works in the body to counteract the effects that APOE4 has.
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Re: Bumetanide for APOE4 Carriers

Post by NF52 »

antimatter37 wrote:Interesting article in "Nature Aging". In this research done by the Gladstone Institute, bumetanide, a common diuretic was found to reduce the instance of AD in APOE4 carriers....
The above is from a review on NIH.Gov:

https://www.nih.gov/news-events/news-re ... -treatment

Kind of an amazing result in some ways if it can be verified. One wonders how this diuretic works in the body to counteract the effects that APOE4 has.
Thanks for sharing an exciting article! When the director of the National Institute on Aging, the major source of U.S. funding on AD research, comments on a study, it's worth noting. This is from the link you shared:
Though further tests and clinical trials are needed, this research underscores the value of big data-driven tactics combined with more traditional scientific approaches to identify existing FDA-approved drugs as candidates for drug repurposing to treat Alzheimer’s disease,” said NIA Director Richard J. Hodes, M.D.
FWIW, the contact for this article is Dr. Yadong Huang, of UCSF, whose team at Gladstone specializes in studying ApoE4. This is one of those studies that is almost certain to lead to follow-on funding for studies to figure out if Bumetanide does in fact show safety and efficacy for ApoE4 carriers.

For $8.99 you can "rent" the article for 24 hours using the link at the bottom of the abstract: Experimental and real-world evidence supporting the computational repurposing of bumetanide for APOE4-related Alzheimer’s disease.

Here's some support in the article for the view that ApoE 3/4 and 4/4 act very differently in the brain than ApoE 3/3: The researchers found 8 pathways to Alzheimer's disease (AD) of "perturbed" up-regulated or down-regulated genes that were "uniquely significantly enriched in ApoE4/4 AD". Two other pathways were uniquely significantly enriched in ApoE 3/4 AD and 58 were uniquely significantly enriched in ApoE3/3 AD.
Only seven pathways were shared across all three groups.
More evidence that Alzheimer's is not one disease, but a syndrome with heterogeneous causes and pathways.

According to the article, Bumetanide has been studied for autism, schizophrenia, seizures and depression, "suggesting brain penetration and potential effectiveness in the central nervous system" by "flipping" genes back from an up-regulated or down-regulated state to a more normal state. In the experiments using a mouse model with ApoE4, the Bumetanide "rescued" neuronal plasticity in the hippocampus and spatial learning. Three pathways that appeared to be significantly affected by the drug were the "GABAergic synapse, circadian entrapment and morphine addiction pathways."

Thanks again for finding and sharing this!
4/4 and still an optimist!
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Re: Bumetanide for APOE4 Carriers

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antimatter37 wrote: Mon Oct 11, 2021 4:41 pmInteresting article in "Nature Aging". In this research done by the Gladstone Institute, bumetanide, a common diuretic was found to reduce the instance of AD in APOE4 carriers....
The above is from a review on NIH.Gov:

https://www.nih.gov/news-events/news-re ... -treatment

Kind of an amazing result in some ways if it can be verified. One wonders how this diuretic works in the body to counteract the effects that APOE4 has.
NF52 wrote: Tue Oct 12, 2021 12:54 pm FWIW, the contact for this article is Dr. Yadong Huang, of UCSF, whose team at Gladstone specializes in studying ApoE4. This is one of those studies that is almost certain to lead to follow-on funding for studies to figure out if Bumetanide does in fact show safety and efficacy for ApoE4 carriers.
I wish we could like posts on the forum -- I find so many articles referenced on the forum and subsequent discussions helpful, but I rarely pause to thank the contributors. :geek: :!:

I wonder if this medication would be helpful for apoe4 carriers who don't need a diuretic -- or if it's benefits may be limited to those with fluid retention and/or inflammation issues? The range of studies on bumetanide is fascinating!

FWIW, I have noticed that after a few months of drinking silica water (in addition to taking curcumin & other supplements), that the fluid-retention I experienced previously has lessened significantly. That particular outcome has been similar to what I experienced on a ketogenic diet. Thanks to Laurie for the encouragement!
laurie wrote:Sun May 05, 2019 11:40 am Drinking silica rich mineral water is such a simple lifestyle choice to implement and one which can improve everyone's health as we are exposed to so much aluminum in our daily lives.
Looking forward to reading & learning more. Thanks NF52 & antimatter37:)
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Re: Bumetanide for APOE4 Carriers

Post by laurie »

cAngelS you are welcome and thanks for the information on changes you have seen from drinking silica water. In case others reading this aren't aware, the form of silica found in some mineral waters is effective at removing aluminum from the body. Why might the outcome of drinking silica rich water be similar to Keto diet? Aluminum inhibits the first step of carbohydrate metabolism called glycolysis. Inhibition of glycolysis promotes the conversion of carbohydrates to stored fats (e.g. lipogenesis). Aluminum inhibits the biosynthesis of L-carnitine. L-carnitine is required for mobilizing stored fat as long chain triglycerides for mitochondrial energy production. By lowering aluminum levels in your body, glycolysis and fat metabolism will return to normal.
"True prevention is only possible by first discovering the cause of a disease such as Alzheimer's."
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Re: Bumetanide for APOE4 Carriers

Post by NF52 »

CAngelS wrote: Thu Jan 06, 2022 10:57 am...
I wish we could like posts on the forum -- I find so many articles referenced on the forum and subsequent discussions helpful, but I rarely pause to thank the contributors. :geek: :!:...
Looking forward to reading & learning more. Thanks NF52 & antimatter37:)
Thanks for taking the time to post! Life is busy; I also have not thanked posters enough--so you've made me realize I should do that more in 2022.
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