Review: NAD+ in Alzheimer’s Disease

[BrianR]

Open access review: https://www.frontiersin.org/articles/10 ... 68491/full

NAD+ in Alzheimer’s Disease: Molecular Mechanisms and Systematic Therapeutic Evidence Obtained in vivo
Wang X, He H-J, Xiong X, Zhou S, Wang W-W, Feng L, Han R and Xie C-L.
Front. Cell Dev. Biol. 9:668491.
DOI: 10.3389/fcell.2021.668491

Mitochondria in neurons generate adenosine triphosphate (ATP) to provide the necessary energy required for constant activity. Nicotinamide adenine dinucleotide (NAD+) is a vital intermediate metabolite involved in cellular bioenergetics, ATP production, mitochondrial homeostasis, and adaptive stress responses. Exploration of the biological functions of NAD+ has been gaining momentum, providing many crucial insights into the pathophysiology of age-associated functional decline and diseases, such as Alzheimer’s disease (AD). Here, we systematically review the key roles of NAD+ precursors and related metabolites in AD models and show how NAD+ affects the pathological hallmarks of AD and the potential mechanisms of action. Advances in understanding the molecular roles of NAD+-based neuronal resilience will result in novel approaches for the treatment of AD and set the stage for determining whether the results of exciting preclinical trials can be translated into the clinic to improve AD patients’ phenotypes.

Editorial: My sense (and I don't know why you'd trust it) of the use and mechanism of NAD+ is that science hasn't yet arrived at a point where you could reliably expect to drug yourself (via OTC supplements or otherwise) and get consistent, well-defined positive results for AD or much of anything else. (Although I have enormous respect for the power of the placebo effect and if you could find a mechanism to causes your body to get to your desired result, that's great.)

Anyway, the author's perspective starts at Future Perspectives and might be worth reading even if you don't want to look through the various results considered in the body of the paper.

[circular]

Open access review: https://www.frontiersin.org/articles/10 ... 68491/full

NAD+ in Alzheimer’s Disease: Molecular Mechanisms and Systematic Therapeutic Evidence Obtained in vivo
Wang X, He H-J, Xiong X, Zhou S, Wang W-W, Feng L, Han R and Xie C-L.
Front. Cell Dev. Biol. 9:668491.
DOI: 10.3389/fcell.2021.668491

Mitochondria in neurons generate adenosine triphosphate (ATP) to provide the necessary energy required for constant activity. Nicotinamide adenine dinucleotide (NAD+) is a vital intermediate metabolite involved in cellular bioenergetics, ATP production, mitochondrial homeostasis, and adaptive stress responses. Exploration of the biological functions of NAD+ has been gaining momentum, providing many crucial insights into the pathophysiology of age-associated functional decline and diseases, such as Alzheimer’s disease (AD). Here, we systematically review the key roles of NAD+ precursors and related metabolites in AD models and show how NAD+ affects the pathological hallmarks of AD and the potential mechanisms of action. Advances in understanding the molecular roles of NAD+-based neuronal resilience will result in novel approaches for the treatment of AD and set the stage for determining whether the results of exciting preclinical trials can be translated into the clinic to improve AD patients’ phenotypes.

Editorial: My sense (and I don't know why you'd trust it) of the use and mechanism of NAD+ is that science hasn't yet arrived at a point where you could reliably expect to drug yourself (via OTC supplements or otherwise) and get consistent, well-defined positive results for AD or much of anything else. (Although I have enormous respect for the power of the placebo effect and if you could find a mechanism to causes your body to get to your desired result, that's great.)

Anyway, the author's perspective starts at Future Perspectives and might be worth reading even if you don't want to look through the various results considered in the body of the paper.

Thanks for all this Brian.

I only skimmed this a little, but this bit popped out: 'Dietary treatment of NR 250 mg/kg/day for 3 months in Tg2576 AD mouse model …', hmmm, let's see, then I would need to take over 13 gm/day to get the equivalent unless I'm missing something?

[BrianR]

I only skimmed this a little, but this bit popped out: 'Dietary treatment of NR 250 mg/kg/day for 3 months in Tg2576 AD mouse model …', hmmm, let's see, then I would need to take over 13 gm/day to get the equivalent unless I'm missing something?

Mice are different. Here's a random paper which discusses converting between animal and human dosages:

A simple practice guide for dose conversion between animals and human

So, if I understand the conversion paper, you would calculate the human effective dose as something like:

250(mg/kg/day) * .081 * body weight(kg) / 1000 (mg/kg) => dosage(mg/day)

so, for some who weighs 65kg:

250mg * 0.081 * 65kg / 1000mg/kg => 1.3 mg/day

Not that I would trust my ability to do math anymore ... Also, i barely skimmed the article, and maybe I misinterpreted Table 1, or perhaps the part about surface area that I zipped right past is actually relevant to this conversion.

Of course, I really wouldn't want to self-dose based on a mouse model study.

[circular]

I only skimmed this a little, but this bit popped out: 'Dietary treatment of NR 250 mg/kg/day for 3 months in Tg2576 AD mouse model …', hmmm, let's see, then I would need to take over 13 gm/day to get the equivalent unless I'm missing something?

Mice are different. Here's a random paper which discusses converting between animal and human dosages:

A simple practice guide for dose conversion between animals and human

So, if I understand the conversion paper, you would calculate the human effective dose as something like:

250(mg/kg/day) * .081 * body weight(kg) / 1000 (mg/kg) => dosage(mg/day)

so, for some who weighs 65kg:

250mg * 0.081 * 65kg / 1000mg/kg => 1.3 mg/day

Not that I would trust my ability to do math anymore ... Also, i barely skimmed the article, and maybe I misinterpreted Table 1, or perhaps the part about surface area that I zipped right past is actually relevant to this conversion.

Of course, I really wouldn't want to self-dose based on a mouse model study.

Thanks for breaking that down BrianS!