Abstract #0691

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

Anshuman Swain¹, Narayan Datt Soni², Ravi Prakash Reddy Nanga², James G Davis³, Halvor Juul², Joeseph A Baur³, and Ravinder Reddy²

¹Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States, ²Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States, ³Department of Physiology, University of Pennsylvania, Philadelphia, PA, United States

Synopsis

Keywords: Biomarkers, Alzheimer's Disease

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.

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