Effect of nicotinamide riboside on glutamate in a 5XFAD mouse model of Alzheimer’s disease as measured by glutamate CEST MRI

Motivation: Nicotinamide riboside (NR) supplementation has increased in popularity for treating neurodegenerative diseases and is attributed to elevated NAD+ levels. Effective monitoring of NR-mediated changes may highlight metabolic underpinnings of NR in dementia. Goal(s): This study uses glutamate-CEST MRI to monitor changes in glutamate levels following NR supplementation in wild-type and 5XFAD mouse models of AD. Approach: Mice (WT and AD) were treated with NR or a vehicle (placebo) for 12 weeks followed by GluCEST MRI. Results: There was a significant GluCEST increase in AD mice compared to WT. Following NR, GluCEST decreased in AD mice, primarily in the hippocampus. Impact: NR supplementation may help alleviate excitotoxicity in AD, thereby preventing neuronal cell death/degeneration. GluCEST provides an effective method for assessing changes in glutamate levels, allowing for monitoring excitotoxicity in patients presenting symptoms of AD and the effects of NR treatment.