Ca:Mg ratio may affect APOE phenotype

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frankiesfriend
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Ca:Mg ratio may affect APOE phenotype

Postby frankiesfriend » Sat May 02, 2020 5:44 pm

Two interesting papers in preprint in the Journal of Alzheimer’s Disease may be of interest to the APOE4 community:


Ca:Mg Ratio, APOE Cytosine Modifications, and Cognitive Function: Results from a Randomized Trial

Xiangzhu Zhua, Amy R. Borensteinb,∗, Yinan Zhengc, Wei Zhangc, Douglas L. Seidnerd,
Reid Nessd, Harvey J. Murffe, Bingshan Lif , Martha J. Shrubsolea, Chang Yug, Lifang Houc
and Qi Daia,∗

Accepted 17 February 2020
The authors sought to test the hypothesis that actively reducing the Ca:Mg intake ratio in the diet through Mg supplementation improves cognitive function, and to test whether this effect is partially mediated by modified cytosines in APOE in a RCT with 250 participants at Vanderbilt University Medical Center.

They report that reducing the Ca:Mg ratio through magnesium supplementation improved cognitive function by 9.1% in participants over 65 years old (but not in those younger) who consumed a high Ca:Mg ratio diet. They observed that in this age group, the beneficial effect of reducing the Ca:Mg ratio was partially mediated by a reduction in DNA methylation markers in APOE (APOE cytosine modifications 5-mC, 5-hmC).

This study did not identify specific APOE genotypes; however, the authors state that, due to the important role of APOE in calcium regulation and the APOE4 disregulation of calcium, “These findings suggest that we may be able to modify the phenotype of APOE variants through modification of 5-mC methylation.”

They state that the optimum Ca:Mg ratio is 2.3 or less, and state that in a previous paper they published results showing that the Ca:Mg ratio should be greater or equal to 1.7 for heart health...thus the desirable ratio is between 1.7 and 2.3, achievable through Mg supplementation.


Review: Is Alzheimer’s Disease a Liver Disease of the Brain?

Accepted 27 February 2020

Margaret F. Bassendinea,b,∗, Simon D. Taylor-Robinsonb, Michael Fertlemanb,c, Michael Khand
and Dermot Neelya,

(This review is long and they have a lot to say, some of which is beyond my understanding, but this is the essence of the review…at least as far as I can determine.)

This article focuses on the role of the liver and lipid homeostasis in the development of AD by regulating the steady-state level of A-beta in the brain (via transfer to the periphery and uptake by LRP-1 in the liver. “We present evidence suggesting that the liver is the origin of brain A-Beta deposits in the brain, and that it is involved in peripheral clearance of circulating amyloid in the blood. Hence the liver could be targeted to decrease A-beta production or increase peripheral clearance” (long before clinical indications of AD).

The authors suggest the following therapeutic agents to increase peripheral clearance of amyloid:

A number of FDA approved drugs used for cholestatic liver disease, diabetes, and lymphoma have demonstrated amyloid –beta clearance in mice. Several of these are in clinical trials for neurodegenerative disease.

They suggest that the isoflavone Genistein, and the flavonoid Silymarin (from milk thistle) have potential for treatment of AD if clinical trials in humans reproduce data obtained in mouse studies.
E3/E4, but still optimistic

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