Nicotinamide Riboside restores cognition in Alzheimer’s mouse models

Studies have suggested that NAD+ mediates multiple major biological processes, including calcium homeostasis, energy metabolism, mitochondrial functions, cell death, and aging in various tissues including the brain. Increasing evidence indicates that NAD+ might play an important roles in metabolic processes in the brain, and has effects on brain functioning such as neurotransmission, learning, and memory.

The activation of NAD expression has been linked with a decrease in the amyloid toxicity in Alzheimer’s disease (AD) animal models in some studies.  This is believed to be connected to the expression of peroxisome proliferator-activated receptor-γ coactivator 1 (PGC)-1α and through the activation of neuronal NAD-dependent deacetylase sirtuin-1 (SIRT1) activation. Evidence has shown that PGC-1α is a crucial regulator of beta-amyloid (Aβ) generation because it affects β-secretase (BACE1) degradation.

In this study the researchers tested the hypothesis that nicotinamide riboside treatment in an AD mouse model could reduce Aβ toxicity through the activation of PGC-1α-mediated BACE1 degradation.

The experiments were done with Tg2576 AD mice, it is one of the most well characterized, and widely used, mouse models of AD. The mice were fed mice with 250 mg/kg/day of NR for 3 months. Using in vivo behavioral analyses, biochemistry assays,  gene silencing and electrophysiological recording the researchers analyzed the effects of NR supplementation. They reported the supplementation with NR significantly reduces cognitive deterioration and coincides with an increase in the steady-state levels of NAD(+) in the cerebral cortex. It was also observed that NR treatment indeed promotes PGC-1α expression in the brain coinciding with enhanced degradation of BACE1 and the reduction of Aβ production in Tg2576 mice. Further in vitro studies confirmed the in vivo observations.

Overall the results suggest that dietary treatment with NR might benefit Alzheimer’s disease cognitive function by preventing Aβ production in the brain.

For perspective on usability in humans we calculate the Human Equivalent Dose (HED) for the nicotinamide riboside diet given to the mice. The FDA has specified guidelines for this conversion to Human Equivalent Dose (HED). Using this guideline 250 mg/kg dosing in mice translates into a HED of approx. 20mg/kg. Or into approximately 1.1 gram daily nicotinamide riboside dose for a person weighing 70kg. Typical supplements on the market have serving sizes of 250mg. It should also be noted that this dose is on the high end wrt to side effects and safety and therefore a therapeutic approach likely to be done under medical supervision.

The study can be found here.

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