In Vivo Assessment of Cerebral β-Hydroxybutyrate Metabolism in APPNL-F/NL-F Mouse Model of Alzheimer's Disease using 2H MR Spectroscopy

Motivation: Among all, glucose hypometabolism is a characteristic pathology in Alzheimer’s disease (AD), under such conditions β-Hydroxy butyrate (BHB) can serve as an alternate source of energy. Measurement of BHB metabolism using a sensitive method could serve as a method for early diagnosis of AD. Goal(s): To monitor BHB metabolism in APPNL-F/NL-F mice. Approach: Monitoring cerebral 2H2-Glx labeling in mice following subcutaneous administration of 2H4-BHB using pulse-acquired 2H-MRS. Results: Although rate of cerebral 2H4-BHB uptake was similar in wild type (WT) and AD mice, moderately enhanced labeling of 2H2-Glx was observed in AD mice compared to WT indicates relatively efficient BHB metabolism in AD. Impact: Although BHB metabolism has been monitored in human and rodent brains using PET and 13C-MRS, inherent limitations restrict their clinical translation. Using a safe and sensitive method like 2H-MRS could be helpful in studying BHB metabolism in various neurodegenerative diseases.