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

Bibliographic

Year of Publication:
2019
Contact PI Name:
Wei-Ping Zhang
Contact PI Affiliation:
Department of Pharmacology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang University School of Medicine, Zhejiang, Hangzhou, China
Co-Authors:
Xian Xie, Yi Gao, Min Zeng, Yi Wang, Tao-Feng Wei, Yun-Bi Lu
Primary Reference (PubMED ID):
Funding Source:
National Key R&D Program of China
Natural Science Foundation of Zhejiang Province in China
Public Technology Application Research of Zhejiang Province
National Natural Science Foundation of China
Study Goal and Principal Findings:

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.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Dietary Interventions & Supplements
Therapeutic Agent:
Nicotinamide Ribose
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Species:
Mouse
Model Type:
APPxPS1
Strain/Genetic Background:
C57BL/6J

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Biomarkers
Dose
Formulation
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest

Outcomes

Outcome Measured
Outcome Parameters
Behavioral
Morris Water Maze
Y Maze
Open Field Test
Histopathology
Cortical and Hippocampal Tissue Loss
Brain Regional Volumes
Hippocampal Atrophy
beta Amyloid Load
beta Amyloid Deposits
Biochemical
CD11b
Glial Fibrillary Acidic Protein (GFAP)
Nicotinamide Phosphoribosyltransferase (NAMPT)
Immunochemistry
Ionized Calcium Binding Adaptor Molecule 1 (Iba1)
Glial Fibrillary Acidic Protein (GFAP)
Toxicology
Body Weight