Effects of APOE on nutritional metabolism in dementia

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Ski
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Effects of APOE on nutritional metabolism in dementia

Postby Ski » Wed Jan 16, 2019 8:03 am

Moderator note - I deleted the attached paper (doi:10.1097/MOL.0000000000000566) because our copyright infringement policy prohibits it. Members in jurisdictions for which access to Sci-Hub is legal may want to search for the paper there.

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Julie G
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Re: Effects of APOE on nutritional metabolism in dementia

Postby Julie G » Wed Jan 16, 2019 8:59 am

Thanks, Ski! Rehashing old findings... Anybody see anything new?

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Re: Effects of APOE on nutritional metabolism in dementia

Postby Ski » Wed Jan 16, 2019 12:02 pm

Curious, whats your take on it?

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Re: Effects of APOE on nutritional metabolism in dementia

Postby Julie G » Sat Jan 19, 2019 12:55 pm

Curious, whats your take on it?

The authors seem to be mostly rehashing old information. Yes, E4 carriers do poorly with other interventions known to improve cognition; Omega-3s, MCT, etc. We've talked extensively about these in the past. Newer research suggests that we may need more (or a different form of) Omega-3s to benefit. The MCT work by Henderson to date has only achieved BHB levels of 0.6mM after weeks of supplementation. No wonder the more disadvantaged E4 carriers failed to show effect! Dr. Bredesen's patients, as a comparison point, are endogenously achieving levels of 0.8-4.0mM by using fasting, exercise and a Mediterranean low carb approach as a part of a multifactorial approach. The authors also state that a high fat diet (to the extend that it leads to insulin resistance) worsens cognition for E4 carriers. We have lots of evidence to support this. Of course, insulin resistance is essentially caused by OVER-nutrition so I suppose that any macronutrient ratio in excess would do the same.

For anyone searching for this one, here's the abstract. I did find it on SciHub.
Effects of apolipoprotein E on nutritional metabolism in dementia.
https://www.ncbi.nlm.nih.gov/pubmed/30550413
Abstract
PURPOSE OF REVIEW:
Various groups have explored the effect of apolipoprotein E (APOE) on neurodegeneration through nutritional and metabolic alterations. In this review, we hope to summarize recent findings in humans as well as preclinical APOE models.
RECENT FINDINGS:
Metabolic pathways including lipid metabolism appear to play a large role in the pathophysiology of Alzheimer's disease. Carrier status of the E4 variant of the APOE gene is the strongest genetic risk factor for Alzheimer's disease, and increasing evidence suggests that E4 carriers may respond differently to a host of dietary and metabolic-related treatments. A new appreciation is forming for the role of APOE in cerebral metabolism, and how nutritional factors may impact this role.
SUMMARY:
Considering the role dietary factors play in APOE-associated cognitive decline will help us to understand how nutritional interventions may facilitate or mitigate disease progression.

I find it interesting that one of the authors of this paper, Dr. Angela Hanson is currently running an NIH trial in which some of our members might be participating. You can read about it here. They are essentially trialing a high SFA/high glycemic index meal against a low/low version of the same in E4 carriers. I had a chance to speak with Dr. Hanson about it a year ago. At that time, she was defending the possibility that a high/high diet might benefit us. :shock: This paper seems to indicate that she's changing position... little surprise. The results of this trial (which should yield some interesting data) won't be available until 2020. That said, in general these high/high vs. low/low trials are frustrating. I'd be much more curious to see what a high fat/low carb vs. low fat/high carb trial would yield.

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Re: Effects of APOE on nutritional metabolism in dementia

Postby mike » Sat Jan 19, 2019 9:10 pm

How about low carb, moderate fat, and higher protein as one of the options?
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