Alzheimer’s APOE4 Impairs Myelination through Cholesterol Dysregulation

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Zuben47
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Alzheimer’s APOE4 Impairs Myelination through Cholesterol Dysregulation

Post by Zuben47 »

https://www.genengnews.com/neurological ... egulation/

This is exciting because it gives us a lot more insight into how the APOE$ gene works to make us more susceptible to dementia and it gives scientists a treatment technique to focus on. It's not crazy to think that such a thing could become commercially available within a decade, given that the researchers have already isolated an effective treatment in vito and in mice. In terms of that last point:

The team focused on drugs that affect cholesterol including statins (which suppress synthesis) and cyclodextrin, which aids cholesterol transport. The statins did not have an effect, but applying cyclodextrin to APOE4 oligodendrocyte cultured in a dish reduced accumulation of cholesterol within the cells and improved myelination in co-cultures with neurons. It showed similar effects in APOE4 mice.

Finally, the team treated some APOE4 mice with cyclodextrin, left others untreated, and subjected them all to two different memory tests. The cyclodextrin-treated mice performed both tests significantly better, suggesting an association between improved myelination and improved cognition.

Tsai said a clear picture is emerging in which intervening to correct specific lipid dysregulations by cell type could potentially help counteract APOE4’s contributions to Alzheimer’s pathology.
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Lulu
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Re: Alzheimer’s APOE4 Impairs Myelination through Cholesterol Dysregulation

Post by Lulu »

This article is interesting, thanks for the share. Cyclodextrin is an oligosaccharide, and now I'm wondering if the oligosaccharide products that are available on the market (like FOS, fructooligosaccharide) could be as beneficial. FOS supplementation increases beneficial bifidobacteria, and can also be beneficial for cholesterol regulation (especially for those who have also changed their lifestyle / diet ). A quick google search, and I found the following article:

https://pubmed.ncbi.nlm.nih.gov/26016937/

Conclusions: Fructooligosaccharides intake may have a beneficial effect on lipid metabolism and regulation of serum cholesterol levels in individuals that change their lifestyle. FOS supplementation use in diets may therefore be a strategy for lowering cholesterol.
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TheresaB
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Re: Alzheimer’s APOE4 Impairs Myelination through Cholesterol Dysregulation

Post by TheresaB »

If you found that article interesting, you might find this interesting It was posted on the ApoE4.info Facebook page today.

link to paper:
Lipid Dys-Homeostasis Contributes to APOE4-Associated AD Pathology

Link to the ApoE4.info facebook page:
https://www.facebook.com/apoe4.info
-Theresa
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Lulu
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Re: Alzheimer’s APOE4 Impairs Myelination through Cholesterol Dysregulation

Post by Lulu »

Thank you, Theresa, I will definitely check it out!
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Lulu
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Re: Alzheimer’s APOE4 Impairs Myelination through Cholesterol Dysregulation

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Ok, so I read the article and my first response to it was yikes!! Olive oil is high in oleic acid, which seems to be implicated in the article, and I've come to believe that EVOO is very healthy for Apoe4 carriers. But then I remembered something else that I've read recently about Apoe4 having a blunted PPAR signaling pathway. PPAR are transcription factors that modulate energy metabolism in liver, adipose tissue and muscle. High fat diets can also negatively impact PPAR expression, favoring obesity, insulin resistance and other conditions. HOWEVER (this is the good part) polyphenols found in vegetables are capable of positively modulating this pathway. Polyphenol molecules help maintain or return to a state of enegy homestasis, due to supporting adequate PPAR expression.

So I'm thinking that we Apoe4s just need a ton of veggies and polyphenols, and this will help counteract our blunted PPAR response, and help with lipid homestasis.

https://pubmed.ncbi.nlm.nih.gov/27367676/

file:///C:/Users/Owner/Downloads/fnagi-12-00150.pdf

This is the article that talks about the Apoe4 blunted PPAR response


Just throwing it out there, "food" for thought :-)
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Re: Alzheimer’s APOE4 Impairs Myelination through Cholesterol Dysregulation

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Lulu wrote: Sat Nov 19, 2022 12:05 pm Ok, so I read the article and my first response to it was yikes!! Olive oil is high in oleic acid, which seems to be implicated in the article, and I've come to believe that EVOO is very healthy for Apoe4 carriers. But then I remembered something else that I've read recently about Apoe4 having a blunted PPAR signaling pathway. PPAR are transcription factors that modulate energy metabolism in liver, adipose tissue and muscle. High fat diets can also negatively impact PPAR expression, favoring obesity, insulin resistance and other conditions. HOWEVER (this is the good part) polyphenols found in vegetables are capable of positively modulating this pathway. Polyphenol molecules help maintain or return to a state of enegy homestasis, due to supporting adequate PPAR expression.

So I'm thinking that we Apoe4s just need a ton of veggies and polyphenols, and this will help counteract our blunted PPAR response, and help with lipid homestasis.

https://pubmed.ncbi.nlm.nih.gov/27367676/

file:///C:/Users/Owner/Downloads/fnagi-12-00150.pdf

This is the article that talks about the Apoe4 blunted PPAR response


Just throwing it out there, "food" for thought :-)
Lulu,
Great post!

FYI, for you or anyone interested, this article from our ApoE4.info wiki has a good discussion on polyphenols:
Beneficial (and some negative) Plant/Natural Chemicals
-Theresa
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waltezell
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Re: Alzheimer’s APOE4 Impairs Myelination through Cholesterol Dysregulation

Post by waltezell »

Here's a Forbe's article (part of an 8-part series called "Reimagining Alzheimer's")
https://www.forbes.com/sites/williamhas ... d883265679
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Re: Alzheimer’s APOE4 Impairs Myelination through Cholesterol Dysregulation

Post by Milena24 »

VERY INTERESTING.

How should I go about getting the APOE4 test done?
I'm on United Healthcare Medicaire and the rep im chatting with doesn't leave me feeling confident in getting this covered.

If they dont cover then where would be the best place to get it done and how much should it cost.

Thanks.

BTW just got LDL in at 134 (a bit high).

Total C is 204. I could try the FOS.
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Re: Alzheimer’s APOE4 Impairs Myelination through Cholesterol Dysregulation

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Milena24 wrote: Thu Dec 22, 2022 12:02 pm VERY INTERESTING.

How should I go about getting the APOE4 test done?
I'm on United Healthcare Medicaire and the rep im chatting with doesn't leave me feeling confident in getting this covered.

If they dont cover then where would be the best place to get it done and how much should it cost.

Thanks.

BTW just got LDL in at 134 (a bit high).

Total C is 204. I could try the FOS.
Welcome, Milena24!

Thanks for your post, I think you are correct in assuming your health insurance provider will not cover ApoE4 testing. At this time it seems most don't. You may want to read up on testing on the Thinking About Testing section of the Welcome page. Additionally, you can sign up on the website 23 and Me to get tested. 23andMe provides general DNA testing, including the ApoE4 allele. That's how I found out I was heterozygous for the allele. The process is simple. You register and they send you a test kit which you mail back to them and they'll send your results.

As a welcome intern, I'm here to make sure you are aware of the many resources available to you on this site should you need them once you have completed testing.

A great place to start is the Primer which is written by by a member physician who carries two copies of the APOE-ε4 allele that offers accessible science background and prioritized sensible preventative measures. Other good resources include the search engine on our site, PubMed, and the internet at large. You may find additional information on the WIKI which is searchable and offers information on various ApoE4 topics.

I hope you find the testing process straightforward. Please feel free to post additional questions here, and if you find that you do carry the ApoE4 allele, we are here to help you navigate next steps.

Best wishes for the testing process and beyond.

Warmly,
Kathleen
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