Background: Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer’s disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field.
Methods: Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4.
Digital Object Identifier (DOI)
Farmer, Brandon C.; Williams, Holden C.; Devanney, Nicholas A.; Piron, Margaret A.; Nation, Grant K.; Carter, David J.; Walsh, Adeline E.; Khanal, Rebika; Young, Lyndsay E. A.; Kluemper, Jude; Hernandez, Gabriela; Allenger, Elizabeth J.; Mooney, Rachel; Golden, Lesley R.; Smith, Cathryn T.; Brandon, J. Anthony; Gupta, Vedant A.; Kern, Philip A.; Gentry, Matthew S.; Morganti, Josh M.; Sun, Ramon C.; and Johnson, Lance A., "APOΕ4 Lowers Energy Expenditure in Females and Impairs Glucose Oxidation by Increasing Flux Through Aerobic Glycolysis" (2021). Clinical and Translational Science Faculty Publications. 6.