WAPF "Wise Traditions" Article by Amy Berger

[Russ]

Very good article win the current (Summery 2-14) edition of WAPF "Wise Traditions" Journal article on "Type 3 Diabetes: Metabolic Causes of Alzheimer's" by Amy Berger…

http://www.westonaprice.org/modern-dise ... s-disease/

Lots of good insight on APOE4 and strong logic for ketogenic pathway. But also note that she hasn't picked up on the fat-type issues picked up by others yet (e.g. Gundry). Still, one of the best holistic overviews I've seen.

Here is the author's web site…

http://www.tuitnutrition.com

[Julie G]

Great paper! I particularly appreciated the way Berger carefully tied the E4 allele to each of the multifactorial processes behind AD. Realistically depressing-yes; but also hopeful as she carefully points out that not all homozygotes develop AD. I like that she points towards a dietary solution that addresses the underlying processes.

I applaud her for tying in ApoE4's impaired glucose metabolism years (even decades) before symptoms appear. I've been pointing to THAT specifically as a key reason for E4 carriers to supply the brain with an alternative fuel via a low carb diet, CR, and exercise for a long time

Her reluctance to jump on the "amyloid as trigger" bandwagon takes a measured look at the evidence to date, specifically Big Pharma's failures. We just don't know the exact role it plays yet...leading me to be cautious about trying to completely eradicate it pharmacologically.

I also like that she warns against going VLC, by pointing out our tremendous need for antioxidants. A beautiful companion piece to my HFLC warnings. Perfect timing. Thank you for sharing, Russ.

[MarcR]

Love this paper for all the reasons Russ and Julie cite. I sent it along to my 21-year-old E3/E4 son because of the observation that AD-predicting reductions in the cerebral metabolic rate of glucose can be observed in young E4 carriers. It's a persuasive reason for him to understand the lifelong AD disease process and consider mitigation measures.

That said, for an article so comprehensive, caloric restriction should have been included as one of the arrows in our AD prevention / treatment quiver. I like Julie's simple maxim: "Eat less than you think you need; less often." I think mild CR and IF may be essential for me to maintain a safe lipid profile on a VLCKD.

[Julie G]

I've read the paper several times now and find something new to appreciate each time. I like how Berger details the interaction between the brain and the rest of the body. Researchers once thought the CNS was closed off, but that understanding continues to evolve.

I also loved her analogy of Henderson's/Newport's use of MCT/coconut oil, without addressing the underlying insulin resistance; akin to that of sailing a boat with a hole. It works, as long as you keep bailing the water Amen.

[MarcR]

Amy followed up this weekend to a detailed series of questions left last week in the comments section of her August blog post highlighting her Wise Traditions article. I'm sure many of us follow her excellent blog, but for those who haven't yet come across her work, here's a nice starting point:

http://www.tuitnutrition.com/2015/01/al ... .html#more

(Actually, for those who haven't read the Wise Traditions article linked in Russ' topic starter, THAT would be the best starting point. Its only competition for my favorite AD article is the September Bredesen study.)

[rep]

Amy says

ApoE4 heterozygotes (people with one allele) have a five-fold increased risk of developing AD, and homozygotes (two alleles) are estimated to have a staggering lifetime risk between 50-90 percent.12

I did not think the risk of being 3/4 was five-fold. I thought the risk for a 3/4 was two-fold.

Comments? What is the truth?

[circular]

rep I've seen everything from 2 fold to now 5 fold. Seems everything I read puts it differently from the last thing I read.

[rep]

What risk does 23andme assign most 3/4s here?

[MarcR]

23andMe says 12.6% for me versus 7.2% "Avg. Risk". My ethnic background is Northern European.

[RichardS]

rep I've seen everything from 2 fold to now 5 fold. Seems everything I read puts it differently from the last thing I read.

I looked at the WAPF reference to a 1995 paper which was definitely not more than the 2-fold and 5-fold figures Rep suggested.

A much more recent and large-scale study suggests Rep is on target:

http://www.ncbi.nlm.nih.gov/pubmed/21556001 Free full text available.

Mol Psychiatry. 2011 Sep;16(9):903-7. doi: 10.1038/mp.2011.52. Epub 2011 May 10.
APOE and Alzheimer disease: a major gene with semi-dominant inheritance.

Apolipoprotein E (APOE) dependent lifetime risks (LTRs) for Alzheimer Disease (AD) are currently not accurately known and odds ratios alone are insufficient to assess these risks. We calculated AD LTR in 7351 cases and 10 132 controls from Caucasian ancestry using Rochester (USA) incidence data. At the age of 85 the LTR of AD without reference to APOE genotype was 11% in males and 14% in females. At the same age, this risk ranged from 51% for APOE44 male carriers to 60% for APOE44 female carriers, and from 23% for APOE34 male carriers to 30% for APOE34 female carriers, consistent with semi-dominant inheritance of a moderately penetrant gene. Using PAQUID (France) incidence data, estimates were globally similar except that at age 85 the LTRs reached 68 and 35% for APOE 44 and APOE 34 female carriers, respectively. These risks are more similar to those of major genes in Mendelian diseases, such as BRCA1 in breast cancer, than those of low-risk common alleles identified by recent GWAS in complex diseases. In addition, stratification of our data by age groups clearly demonstrates that APOE4 is a risk factor not only for late-onset but for early-onset AD as well. Together, these results urge a reappraisal of the impact of APOE in Alzheimer disease.

This is based on risk at age 85, so fold-changes might be higher at younger ages. However, I like the use of 85 as an anchor because I see it as more meaningful when talking about "lifetime" risk.