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NAD+ supplementation normalizes key Alzheimer’s features and DNA damage responses in a new AD mouse model

nicotinamide riboside alzheimers

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#1 Kirito

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Posted 07 February 2018 - 07:37 PM


NAD+ supplementation normalizes key Alzheimer’s features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency

Here we report that 3xTgAD/Polβ+/− mice have a reduced cerebral NAD+/NADH ratio indicating impaired cerebral energy metabolism, which is normalized by nicotinamide riboside (NR) treatment. NR lessened pTau pathology in both 3xTgAD and 3xTgAD/Polβ+/− mice but had no impact on amyloid β peptide (Aβ) accumulation. NR-treated 3xTgAD/Polβ+/− mice exhibited reduced DNA damage, neuroinflammation, and apoptosis of hippocampal neurons and increased activity of SIRT3 in the brain. NR improved cognitive function in multiple behavioral tests and restored hippocampal synaptic plasticity in 3xTgAD mice and 3xTgAD/Polβ+/− mice. In general, the deficits between genotypes and the benefits of NR were greater in 3xTgAD/Polβ+/− mice than in 3xTgAD mice. Our findings suggest a pivotal role for cellular NAD+ depletion upstream of neuroinflammation, pTau, DNA damage, synaptic dysfunction, and neuronal degeneration in AD. Interventions that bolster neuronal NAD+ levels therefore have therapeutic potential for AD.

 

http://www.pnas.org/...1/31/1718819115


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#2 able

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Posted 07 February 2018 - 09:45 PM

Encouraging.  Seems like they could/should have mentioned NR in the title.    



#3 Mind

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Posted 07 February 2018 - 10:23 PM

....in mice. Will wait for more human data before getting too excited.


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#4 Harkijn

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Posted 08 February 2018 - 05:27 PM

....in mice. Will wait for more human data before getting too excited.

 

Yes,in mice. Genetically prepared mice at that. But in contrast to many earlier studies, these researchers used 5 groups of mice, One of the control groups consisted of the same AD mice but  not NR treated. In addition to that human AD fibroblasts were NR treated with good results.

The mice went through a slew of tests and the NR treated mice performed very well.

It seems to me that even for mice 12mM in their drinking water is an extremely small amount unless they are very thirsty :-).

 

I add the full study here, because IMHO this study deserves scrutiny by those who know a lot about mice studies.

 

If I had an AD patient in the family, I would start sprinkling NR into their tea or coffee as from today.....

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Edited by Harkijn, 08 February 2018 - 05:30 PM.


#5 tunt01

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Posted 09 February 2018 - 11:01 PM

Can someone confirm to me that I have the conversion right on this intervention?

 

Intervention:  12 mM of NR

 

12 mmol/L * 255.2472 g/mol = 3,062.97 g/L * 1/1000 = 3.06297 mg/mL

 

each mouse is approx. 130 mL/kg in water consumption, therefore 3.06297 mg/mL * 130 mL/kg = 398.1861 mg/kg per day

 

allometric scaling to human is 3/37 or 398.1861 * 3/37 = 32.285 mg/kg for a human.

 

therefore ~70 kg adult is 2,260 mg per day.

 

 


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#6 tunt01

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Posted 10 February 2018 - 01:14 AM

....in mice. Will wait for more human data before getting too excited.

 

There are enough studies at this point, I think.  NR is the real deal.  What the risks are in terms of cancer or altered methylation... who knows.



#7 stefan_001

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Posted 10 February 2018 - 11:48 AM

Can someone confirm to me that I have the conversion right on this intervention?

 

Intervention:  12 mM of NR

 

12 mmol/L * 255.2472 g/mol = 3,062.97 g/L * 1/1000 = 3.06297 mg/mL

 

each mouse is approx. 130 mL/kg in water consumption, therefore 3.06297 mg/mL * 130 mL/kg = 398.1861 mg/kg per day

 

allometric scaling to human is 3/37 or 398.1861 * 3/37 = 32.285 mg/kg for a human.

 

therefore ~70 kg adult is 2,260 mg per day.

 

Looks correct to me, about 2 gram / day. Pity they never try at same time effects at lower dosing.


Edited by stefan_001, 10 February 2018 - 11:49 AM.

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#8 Turnbuckle

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Posted 10 February 2018 - 04:41 PM

One gram nicotinamide and one gram ribose will get you there.

 


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#9 stefan_001

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Posted 10 February 2018 - 06:56 PM

 

One gram nicotinamide and one gram ribose will get you there.

 

 

Please not again, till somebody repeats the study with your proposal and observes the same results you cannot claim that. Its irresponsible.
 


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#10 Turnbuckle

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Posted 10 February 2018 - 07:27 PM

 

 

One gram nicotinamide and one gram ribose will get you there.

 

 

Please not again, till somebody repeats the study with your proposal and observes the same results you cannot claim that. Its irresponsible.
 

 

 

Ah, no. We don't wait for studies here. Especially by partisans.


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#11 MikeDC

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Posted 10 February 2018 - 07:39 PM

Sell your idea to a serious researcher and do a study first.
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#12 Harkijn

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Posted 11 February 2018 - 10:13 AM

Those of us who are (genuinely) interested in NAD+ know that when Vincent Giuliano speaks there is always a lot to learn. I don't think it useful to start new threads all the time, so I point here to his website, just in case you missed his latest article:

http://www.anti-agin...ntation-coming/



#13 stefan_001

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Posted 11 February 2018 - 12:24 PM

Those of us who are (genuinely) interested in NAD+ know that when Vincent Giuliano speaks there is always a lot to learn. I don't think it useful to start new threads all the time, so I point here to his website, just in case you missed his latest article:

http://www.anti-agin...ntation-coming/

 

His stories are a mix of fact and fiction. This is what he has to say about NAD+ supplementation:

 

I am now confidence that supplementation with a NAD+ precursor like NMN or NR transiently increased the ratio of NAD+  to NADH (NAD/NADH), but the ratio returns to normal in the course of continued supplementation.  This is because there is an enzyme that regulates the NAD/NADH ratio.  The ratio is NOT determined by dietary intake or IV intake of any compound.  It is enzymatically controlled. That enzyme is called  “NAD(P)H dehydrogenase, quinone 1″, or NQO1 for short.  NQO1 is an unusual gene in that it requires NADH as a co-factor but does not convert the NADH into nicotinamide, like the Sirtuins or PARPs.  Instead, it converts NADH to NAD+.  (i.e. it only oxidizes NADH to NAD+).
 

In his slides he says this:

7. I strongly conjecture that IV NAD infusions are now the best and possibly only way to provide such a rebooting intervention.  Clinicians who are involved with NAD infusions at this conference have told me that they definitely have noticed a switching process that often takes place as a result of an infusion to a  basically more healthy  constitutional state.

 

He probably gets paid to say this.


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#14 able

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Posted 11 February 2018 - 11:32 PM

"NR lessened pTau pathology in both 3xTgAD and 3xTgAD/Polβ+/− mice but had no impact on amyloid β peptide (Aβ) accumulation"

 

That seems  to be different than the results of the NMN study:

 

"NMN decreased β-amyloid production, amyloid plaque burden, synaptic loss, and inflammatory responses in AD-Tg mice"

 

Both studies seem positive, but can anyone decipher if this is truly a different effect between the two supplements, and if it is relevant or not?

 

Edited by able, 11 February 2018 - 11:34 PM.

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