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

Metab Brain Dis. 2019 Feb;34(1):353-366. doi: 10.1007/s11011-018-0346-8. Epub 2018 Dec 6.

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.

Keywords: Alzheimer’s disease (AD); Cognition; Dementia; Neuroinflammation; Nicotinamide adenine dinucleotide (NAD); Nicotinamide ribose (NR).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / psychology
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Brain / drug effects
  • Brain / metabolism
  • Cognition / drug effects*
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / psychology
  • Disease Models, Animal
  • Memory / drug effects
  • Mice
  • Microglia / drug effects
  • Microglia / metabolism
  • Motor Activity / drug effects
  • Niacinamide / analogs & derivatives*
  • Niacinamide / pharmacology
  • Niacinamide / therapeutic use
  • Nicotinamide Phosphoribosyltransferase / blood

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • nicotinamide-beta-riboside
  • Niacinamide
  • Nicotinamide Phosphoribosyltransferase