new research

[alwayslearning]

Hello everyone, I am a new member as of today. (I am E3/E4) I came across a paper on ApoE diet published 3 days ago that I thought you all might like to read. http://journals.plos.org/plosone/articl ... ne.0148099

[circular]

Welcome alwayslearning! Like your screen name

That paper is both really interesting and mighty confusing. Having just started trialing a ketogenic diet, I'm not sure what to think. Hopefully some of our ketotic friends will offer their perspective.

Good find.

[Stavia]

Hi and welcome.
We'd love to hear more about you.
This is a high level paper, you must be well into the game.
What strategies are you currently favouring?

As regards the paper, I'd like to know exactly what the furry friends were fed before commenting. All fat is certainly not equal. And rodent diets do not always extrapolate well to humans.
Anyone interested in getting full text?

[Julie G]

Welcome, alwayslearning! VERY interesting paper. Thanks for sharing. I know it's difficult to extrapolate from mice to humans, but this looks really promising:

The role of ApoE and its isoforms in the ketogenic state is relatively unknown. In contrast to the high-fat diet, we found no change in hippocampal ApoE levels in response to ketogenic diet for any genotype. However, we did observe an interesting effect of ketogenic diet on plasma ApoE, with ApoE4 mice having a large increase in plasma ApoE in response to ketosis, while ApoE3 mice experienced a more moderate change. [Empasis mine]

We know E4 mice and humans have the lowest levels of ApoE. Could this be a way of boosting it?

[Tincup]

As regards the paper, I'd like to know exactly what the furry friends were fed before commenting. All fat is certainly not equal. And rodent diets do not always extrapolate well to humans.

I certainly agree.

Two interpretations are possible from our findings: either the high-fat diet-induced reduction in ApoE is itself harmful for brain function, or it is a protective adaptive response.

[/quote]
Flip a coin...

For now I'll stick with my 90% vegan keto diet.

[Gilgamesh]

I'm getting the full text from the link -- you all not?

In any event, the keto diet:

75% fat, 8.6% protein, 3.2% carbohydrate, lard- and butter-based, AIN-76A-Modified from Bio Serv

Yum yum! Lard!!

Not healthful, but we certainly cannot assume that healthy fats would produce a different result with respect to APOE levels, specifically. Type of fat may not matter for that.

G

[Stavia]

Wow. 75%. Saturated fat.
Why would a human eat that?

[Gilgamesh]

Lard aside, I'm realizing this is an extremely useful, interesting paper! I suggest everyone at least read the Discussion section. It contains an exceedingly clear summary of the primary scientific challenges we face in figuring out the relation between macronutrient ratios and APOE-mediated AD risk.

G

[Stavia]

Ah yes the full text was on the site sorry.
Yes, so many questions. Sigh.

But it does demonstrate isoform dependent consequences of different macronutrient dietary composition in mousies. Is the increased or reduced apoe expression relevant for humans? It doesnt tell us *which* macronutrient ratio is best for human e4s.

[Julie G]

Good observations, all. Confusing.

The authors seems to be torn on which route would provide the best Aβ clearance: reducing ApoE or increasing it. A clue might come from APOE-ε4 itself, which has the lowest level of ApoE and the worst rate of clearance. My money is on figuring out a way to increase hippocampal ApoE via diet, lifestyle, pharma or any combination thereof.

A clue?

Surprisingly, in contrast to the wildtype mice, we found that a high-fat diet significantly reduced levels of hippocampal human ApoE in ApoE3 TR mice, but not ApoE4 TR mice.

A warning to APOE-ε3 carriers against high fat diets? Why in the world would one manipulate their ApoE to achieve the APOE levels of ε4 carriers?

In our experiments, we found a similar trend towards reduction of hippocampal ApoE in ApoE4 TR mice, which did not achieve significance. That said, it is tempting propose a model by which a high-fat diet brings levels of ApoE3 down to ApoE4 baseline levels.

Trying to increase ApoE lipidation is very reminiscent of Bexarotene’s mechanism of action. Whatever happened to that?
http://www.alzforum.org/news/research-n ... -pathology