Nicotinamide ribose ameliorates cognitive impairment of aged and Alzheimer’s disease model mice

Abstract

Nicotinamide adenine dinucleotide (NAD) supplementation to repair the disabled mitochondria is a promising strategy for the treatment of Alzheimer’s disease (AD) and other dementia. Nicotinamide ribose (NR) is a safe NAD precursor with high oral bioavailability, and has beneficial effects on aging. Here, we applied NR supplied food (2.5 g/kg food) to APP/PS1 transgenic AD model mice and aged mice for 3 months. Cognitive function, locomotor activity and anxiety level were assessed by standard behavioral tests. The change of body weight, the activation of microglia and astrocytes, the accumulation of Aβ and the level of serum nicotinamide phosphoribosyltransferase (NAMPT) were determined for the evaluation of pathological processes. We found that NR supplementation improved the short-term spatial memory of aged mice, and the contextual fear memory of AD mice. Moreover, NR supplementation inhibited the activation of astrocytes and the elevation of serum NAMPT of aged mice. For AD model mice, NR supplementation inhibited the accumulation of Aβ and the migration of astrocyte to Aβ. In addition, NR supplementation inhibit the body weight gain of aged and APP/PS1 mice. Thus, NR has selective benefits for both AD and aged mice, and the oral uptake of NR can be used to prevent the progression of dementia.

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Acknowledgments

The authors are grateful to the Core Facilities of Zhejiang University Institute of Neuroscience for technical assistance.

This work was supported by grants from the National Key R&D Program of China (2018YFA0507700), the National Natural Sciences Foundation of China (81573400), the Zhejiang Provincial Natural Science Foundation of China (LY18H170001), and Public Technology Application Research of Zhejiang Province (2016F82G2010036).

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Correspondence to Wei-Ping Zhang.

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Xie, X., Gao, Y., Zeng, M. et al. Nicotinamide ribose ameliorates cognitive impairment of aged and Alzheimer’s disease model mice. Metab Brain Dis 34, 353–366 (2019). https://doi.org/10.1007/s11011-018-0346-8

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Keywords

  • Nicotinamide adenine dinucleotide (NAD)
  • Nicotinamide ribose (NR)
  • Alzheimer’s disease (AD)
  • Cognition
  • Dementia
  • Neuroinflammation