APOΕ4 Lowers Energy Expenditure in Females and Impairs Glucose Oxidation by Increasing Flux Through Aerobic Glycolysis

Authors

Brandon C. Farmer, University of Kentucky
Holden C. Williams, University of Kentucky
Nicholas A. Devanney, University of Kentucky
Margaret A. Piron, University of Kentucky
Grant K. Nation, University of Kentucky
David J. Carter, University of Kentucky
Adeline E. Walsh, University of Kentucky
Rebika Khanal, University of Kentucky
Lyndsay E. A. Young, University of Kentucky
Jude Kluemper, University of Kentucky
Gabriela Hernandez, University of Kentucky
Elizabeth J. Allenger, University of Kentucky
Rachel Mooney, University of Kentucky
Lesley R. Golden, University of Kentucky
Cathryn T. Smith, University of Kentucky
J. Anthony Brandon, University of Kentucky
Vedant A. Gupta, University of Kentucky
Philip A. Kern, University of Kentucky
Matthew S. Gentry, University of Kentucky
Josh M. Morganti, University of Kentucky
Ramon C. Sun, University of Kentucky
Lance A. Johnson, University of Kentucky

Abstract

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.

Document Type

Article

Publication Date

12-2021

Digital Object Identifier (DOI)

10.1186/s13024-021-00483-y

Repository Citation

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.
https://uknowledge.uky.edu/ccts_facpub/6