Raising NAD+ levels in the brain restores cognition in rats with Alzheimer’s disease

Alzheimer’s disease (AD) is most prominently characterized by the accumulation of amyloid plaques and neurofibrillary tangles. The beta-amyloid (Aβ) oligomers are seen as neurotoxic agents. There is evidence from previous research that maintaining cell metabolism, activation of NAD+ expression, may stall or decrease beta-amyloid (Aβ) toxicity in AD. This motivated a combined Chinese and Japanese research team to study the effect of administration of a NAD+ precursor on the progression of Alzheimer’s disease in rats.

AD model rats were injected intraperitoneally with NMN (500mg/kg) and subjected to cognition tests. The so called Morris water maze test indicated that the treatment brought sustained improvement in cognitive function.

In-vitro the reseachers prepared cultured hippocampal slices to analyze the impact of the NAD+ precursor NMN on Aβ plaque induced neuronal death and cognitive impairment. They found that treatment with NMN attenuated neuronal cell death. The NMN treatment also significantly prevented the Aβ oligomer-induced inhibition of Long Term Potentiation (LTP). LTP is a persistent increase in synaptic strength following high-frequency stimulation of a synapse. Improved LTP in the hippocampus may indicate improved learning and memory ability. These studies of LTP are often carried out in slices of the hippocampus as was also done in this study

Furthermore, NMN restored levels of NAD+ and ATP, eliminated accumulation of reactive oxygen species (ROS) in the Aβ plaque – treated hippocampal slices. The positive effects were reversed when applying a compound (3-acetylpyridine) that inactivates NAD+, this observation adds to the notion that NAD+ is responsible for the protective effects seen.

Overall this study indicates that NMN could restore cognition in AD model rats and may have future therapeutic drug for AD.

With the main mechanism of action the boosting of NAD+ it can be speculated this study also supports the effectiveness of other NAD+ pre-cursors like nicotinamide riboside which has been proven to raise NAD+ levels in blood  by dietary supplementation as opposed to the injected, high cost, NMN.

The study can be found here.

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