Cholesterol drives Alzheimer's plaque formation

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Cholesterol drives Alzheimer's plaque formation

Postby NewRon » Wed Sep 15, 2021 3:53 am

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Julie G
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Re: Cholesterol drives Alzheimer's plaque formation

Postby Julie G » Wed Sep 15, 2021 8:28 am

Interesting. From what I understood, cholesterol in the brain is only a problem when efflux is hampered as is often the case with E4s. Interestingly, plasmalogens appear to normalize efflux and are correlated with reduced amyloid-beta.

But wait, there's more. ;) I just stumbled upon this tidbit today suggesting that amyloid-beta is primarily created in the liver??? https://www.newsbreak.com/news/23707915 ... Site&ss=i4

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Re: Cholesterol drives Alzheimer's plaque formation

Postby JulieAnnie » Wed Sep 15, 2021 2:02 pm

Further down that rabbit hole Julie, which you just opened, has been an overlooked amyloid, Islet Amyloid Polypeptide (IAPP). IAPP is co-produced in the pancreas islet cells along with insulin. They are co-released by the pancreas in a 10 to 1(IAPP) ratio. IAPP has been studied as a target for AD because of its propensity to misfold and aggregate. Recent studies have hypothesized that this peptide is now considered a contributing factor to AD. As a Type 1 diabetic (21 years), I've been following this for many years because my pancreas no longer produces insulin or IAPP and I wondered what, if any, impact that might have on my brain. If you carry this forward to Type 2 diabetics who are insulin resistant, they produce large amounts of insulin and IAPP. IAPP has been found to cause BBB damage, microglia activation and cross seeding. In normal amounts, IAPP delays gastric emptying and acts as a satiety agent. It's complicated but does make sense with insulin resistance being a risk factor for AD. Here is a recent paper on the subject:

[url][/url]Ferreira S, Raimundo AF, Menezes R, Martins IC. Islet amyloid polypeptide & amyloid beta peptide roles in Alzheimer's disease: two triggers, one disease. Neural Regen Res. 2021 Jun;16(6):1127-1130. doi: 10.4103/1673-5374.300323. PMID: 33269760; PMCID: PMC8224102.[url][/url]

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Re: Cholesterol drives Alzheimer's plaque formation

Postby SBee » Wed Sep 15, 2021 4:33 pm

Julie G wrote:Interesting. From what I understood, cholesterol in the brain is only a problem when efflux is hampered as is often the case with E4s. Interestingly, plasmalogens appear to normalize efflux and are correlated with reduced amyloid-beta.

But wait, there's more. ;) I just stumbled upon this tidbit today suggesting that amyloid-beta is primarily created in the liver??? https://www.newsbreak.com/news/23707915 ... Site&ss=i4


Julie,
As I am just becoming familiar with much of the AD research and various interventions for prevention, this quote from the article has left me a bit confused:
In addition, dietary modifications such as lowering consumption of high-fat foods, could "potentially" slow production of these proteins [amyloid-beta] in the liver, thus reducing blood levels and preventing them from accumulating in the brain, he said.
As I understand it, one of the primary research-based strategies that has been discussed on this site to help prevent AD, is consuming a mild ketogenic diet which incorporates low carb and higher fat/protein foods. I've been eating lots of avocado, olive oil, nuts, seeds and fatty fish!! Perhaps it comes down to the fact that we each need to find the right balance of macronutrients based on our individual needs?
Interesting thread!
Thanks,
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Re: Cholesterol drives Alzheimer's plaque formation

Postby Julie G » Wed Sep 15, 2021 6:45 pm

Julie,
As I am just becoming familiar with much of the AD research and various interventions for prevention, this quote from the article has left me a bit confused:
In addition, dietary modifications such as lowering consumption of high-fat foods, could "potentially" slow production of these proteins [amyloid-beta] in the liver, thus reducing blood levels and preventing them from accumulating in the brain, he said.
As I understand it, one of the primary research-based strategies that has been discussed on this site to help prevent AD, is consuming a mild ketogenic diet which incorporates low carb and higher fat/protein foods. I've been eating lots of avocado, olive oil, nuts, seeds and fatty fish!!

Hi Sue! That struck me as well but I suspect that it's based on an outdated understanding of dietary/lipid interactions. As we know from our own N=1s and watching other members using a LCHF approach, our triglycerides tend to drop (not rise) with with higher fat as long as we concurrently reduce sugar and starchy carbs. As you'll recall from the article, amyloid was carried by triglycerides. This confirms other research suggesting that low triglycerides appear to be protective against Alzheimer's.
In the mice, the researchers saw that the protein was carried in the blood by triglyceride-rich lipoproteins, which are also produced by the liver, to the brain, just as they do in humans.

Triglyceride-rich lipoproteins are also known to spread triglycerides, a type of cholesterol, from the digestive system to the bloodstream, where it travels throughout the body, potentially damaging organs such as the brain and heart.

Mice with high levels of both amyloid and triglyceride-rich lipoproteins experienced neurodegeneration -- or the loss of structure and function of brain cells -- and brain atrophy, or wasting away, according to the researchers.

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Re: Cholesterol drives Alzheimer's plaque formation

Postby SBee » Wed Sep 15, 2021 7:12 pm

Julie,
Thank you for clarifying this point with the added information from the article! Appreciate your response:)
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Re: Cholesterol drives Alzheimer's plaque formation

Postby NewRon » Fri Sep 17, 2021 1:23 pm

Thanks, this is SO interesting!
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Re: Cholesterol drives Alzheimer's plaque formation

Postby circular » Wed Oct 06, 2021 8:25 pm

Julie G wrote:Hi Sue! That struck me as well but I suspect that it's based on an outdated understanding of dietary/lipid interactions. As we know from our own N=1s and watching other members using a LCHF approach, our triglycerides tend to drop (not rise) with with higher fat as long as we concurrently reduce sugar and starchy carbs. As you'll recall from the article, amyloid was carried by triglycerides. This confirms other research suggesting that low triglycerides appear to be protective against Alzheimer's.

Hi Julie, I'm just noodling this a bit without justification, given that I haven't read the whole thread. I was asking myself what happens if a high fat diet does increase the liver's output of AB while also reducing TGs. What then happens to the increased AB???

There is an ancient history paper, originally published on papyrus, from 2008, Hippocampal RAGE Immunoreactivity in Early and Advanced Alzheimer’s Disease, that says:
Because of its molecular structure and nature, RAGE [receptor for advanced glycation end products] has been under scrutiny for its potential role in mediating circulating plasma Aβ across the BBB and into the brain, where its deposition is seen in AD pathogenesis..

Increased expression of RAGE is reported to be associated with several pathological states, including Alzheimer’s disease, diabetic nephropathy, and immune/inflammatory reactions of the vessel walls

I haven't been able to figure out whether this potential process still requires triglycerides to carry the AB to the RAGE or whether it's an independent pathway that AB takes into the brain, and the links to the original article posted earlier in this thread aren't working for me to see what they said.
ApoE 3/4 > Thanks in advance for any responses made to my posts.

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Re: Cholesterol drives Alzheimer's plaque formation

Postby Julie G » Thu Oct 07, 2021 9:02 am

I was asking myself what happens if a high fat diet does increase the liver's output of AB while also reducing TGs. What then happens to the increased AB???

Dumb question, but what evidence do you have that a high fat diet increases the liver's output of AB? The study I linked was a mouse study. The natural diet of a mouse is LFHC and lots of toxic effects occur when switching that up. Humans, on the other hand, have a wide tolerance for multiple dietary path's as outlined in BrianR's recent thread. You may know of other research that backs up your assumption. I look forward to learning more.

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Re: Cholesterol drives Alzheimer's plaque formation

Postby circular » Thu Oct 07, 2021 9:44 am

Julie G wrote:
Circular wrote:I was asking myself what happens if a high fat diet does increase the liver's output of AB while also reducing TGs. What then happens to the increased AB???

Dumb question, but what evidence do you have that a high fat diet increases the liver's output of AB? … You may know of other research that backs up your assumption.

I may have misread or misinterpreted the earlier interchange between you and SBee to suggest that high fat diets increase the liver's output of AB. Maybe I also should have used emphases to make clearer that I wasn't assuming that's the case, so my question would have read:
What happens if a high fat diet does increase the liver's output of AB while also reducing TGs. What then happens to the increased AB???

But even with the emphases, if no one is claiming that a high fat diet increases the liver's output of AB, then consider my question null and void, if not me too :lol: ;)
ApoE 3/4 > Thanks in advance for any responses made to my posts.


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