new research

[Russ]

Seems to me that although less emphasized in the article, perhaps even more significant than reduction in hippocampal APOE levels on high fat diet - esp for E3's - is the observation that plasma APOE levels are very substantially increased on ketogenic diet and differentially so for E4's.

I've put all the data on one pair of charts for ease of understanding....

Slide1.jpg

Potential significance and implications?

[J11]

Now that is very interesting!
I have been trying all day to remember what greatly moved up APOE levels.
Thank you for the reminder: Ketogenesis!

Might this be why Axona works best in APOE e3s?

Would be very very interested to see what might happen with the triple
combo treatment of ketosis, DHA and bexarotene.

[circular]

A landmark n=1 review concludes I'm more confused than ever.

[Russ]

OK, this study seems relevant to my above comment....

http://www.medscape.com/viewarticle/812097

"We found that low plasma levels of APOE associate with risk of dementia, and we found that low plasma levels of APOE associate with risk of dementia independent of APOE gene type," Dr. Rasmussen concluded.

Could it be that driving up plasma levels of APEO is key for us E4's in combination with some kind of equilibrium/non-suppressed levels in the brain?

PS: Would LOVE to see this same (originally linked) study repeated for different industrial vs natural (pastured/grassfed) fat (e.g. lard, tallow, butter) sources.

Russ

[Julie G]

Great graph- Russ, Thank you! Visually seeing the evidence is very helpful. Perhaps the plasma vs. hippocampal APOE is a red herring given this strong association (between plasma APOE and dementia) in humans from your link?

When the nearly 76,000 participants were divided into APOE tertiles, the cumulative incidence of Alzheimer's disease with age was significantly associated with APOE level.

"We found a 3-fold increased risk for the lowest tertile versus the highest tertile and a highly significant P [value] for trend, and the association remained after further adjustment for the APOE genotype," Dr. Rasmussen reported (log-rank trend P < .001).

I seem to recall multiple papers concluding the same with regard to the association between APOE levels and risk of dementia. I'll poke around and see what I can find...

[LG1]

You guys are awesome!

I found the article myself this evening and so went to to see if anyone was talking about it here and sure enough! This is extremely interesting to me as I am on a keto diet 95% of the time and have been for several months.

Looking forward to more of everyone's input!

Laura

[LG1]

...I couldn't resist sharing this old chestnut from Apolipoprotein E and Alzheimer disease: risk, mechanisms, and therapy. It's a nice graphic summary of both the ApoE4 loss of function AND toxic gain-of-function

nihms492068f3.gif

Thanks for the link to the article, Julie...

Can someone please confirm this says what I think it says?!

The frequency of AD and mean age at clinical onset are 91% and 68 years of age in ε4 homozygotes, 47% and 76 years of age in ε4 heterozygotes, and 20% and 84 years in ε4 noncarriers,7, 20 indicating that APOE ε4 confers dramatically increased risk of development of AD with an earlier age of onset in a gene dose-dependent manner (Figure 1b).

Are they saying 91% of E4/4's will have AD by age 68?

Thanks...........

[LG1]

Seems to me that although less emphasized in the article, perhaps even more significant than reduction in hippocampal APOE levels on high fat diet - esp for E3's - is the observation that plasma APOE levels are very substantially increased on ketogenic diet and differentially so for E4's.

I've put all the data on one pair of charts for ease of understanding....

Slide1.jpg

Potential significance and implications?

Russ, (or Stavia or Julie or anyone else that knows) I'm a little behind the learning curve on this but trying... can you explain what it means for E4/4's? I am confused as to what is considered 'good' on the chart here. Hippocampal APOE levels.... Should they be high or low? Am I right in understanding it is 'good' for the APOE plasma levels to be high?

Thanks!

[J11]

Sorry to take this off topic, though I wanted to see if anyone might make sense of this.

Looks like there is a histidine/histamine deficit in AD.
https://www.ncbi.nlm.nih.gov/pubmed/2713757

Lack of histidine could lead to copper trouble
http://www.ncbi.nlm.nih.gov/pubmed/24435851

[Julie G]

LGI, I try not to overly focus on statistical predictions. They're truly all over the place. If it's any comfort, that 91% is a lifetime risk. It doesn't mean that 91% of us homozygotes will develop AD by age 68.

Russ, (or Stavia or Julie or anyone else that knows) I'm a little behind the learning curve on this but trying... can you explain what it means for E4/4's? I am confused as to what is considered 'good' on the chart here. Hippocampal APOE levels.... Should they be high or low? Am I right in understanding it is 'good' for the APOE plasma levels to be high?

According to Dr. Rasmussen, author of the paper below, low levels of apoE are associated with future risk of developing dementia. This conclusion is based upon an enormous dataset- almost 76,000 people...quite impressive. This paper has been cited by 10 others. Scroll to the bottom of the link above to see them.

Plasma Levels of Apolipoprotein E and Risk of Dementia in the General Population
https://www.researchgate.net/publicatio ... Population

J11, thanks. I'm looking forward to following up on those links!