Medicine and Health Sciences Commons^™

Apoε4 Lowers Energy Expenditure In Females And Impairs Glucose Oxidation By Increasing Flux Through Aerobic Glycolysis, Brandon C. Farmer, Holden C. Williams, Nicholas A. Devanney, Margaret A. Piron, Grant K. Nation, David J. Carter, Adeline E. Walsh, Rebika Khanal, Lyndsay E. A. Young, Jude C. Kluemper, Gabriela Hernandez, Elizabeth J. Allenger, Rachel Mooney, Lesley R. Golden, Cathryn T. Smith, J. Anthony Brandon, Vedant A. Gupta, Philip A. Kern, Matthew S. Gentry, Josh M. Morganti, Ramon C. Sun, Lance A. Johnson

Physiology Faculty Publications

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.

RESULTS: Single-cell …

Novel Influences Of Sex And Apoe Genotype On Spinal Plasticity And Recovery Of Function After Spinal Cord Injury, Lydia E. Strattan, Daimen R. Britsch, Chris M. Calulot, Rachel S. J. Maggard, Erin L. Abner, Lance A. Johnson, Warren J. Alilain

Sanders-Brown Center on Aging Faculty Publications

Spinal cord injuries can abolish both motor and sensory function throughout the body. Spontaneous recovery after injury is limited and can vary substantially between individuals. Despite an abundance of therapeutic approaches that have shown promise in preclinical models, there is currently a lack of effective treatment strategies that have been translated to restore function after SCI in the human population. We hypothesized that sex and genetic background of injured individuals could impact how they respond to treatment strategies, presenting a barrier to translating therapies that are not tailored to the individual. One gene of particular interest is APOE, which has …

Polygenic Score Modifies Risk For Alzheimer's Disease In Ε4 Homozygotes At Phenotypic Extremes, Aamira J. Huq, Brian Fulton-Howard, Moeen Riaz, Simon Laws, Robert Sebra, Joanne Ryan, Alzheimer’S Disease Genetics Consortium, Alan E. Renton, Alison M. Goate, Colin L. Masters, Elsdon Storey, Raj C. Shah, Anne Murray, John Mcneil, Ingrid Winship, Paul A. Jones

Research outputs 2014 to 2021

Introduction: Diversity in cognition among apolipoprotein E () ε4 homozygotes can range from early-onset Alzheimer's disease (AD) to a lifetime with no symptoms. Methods: We evaluated a phenotypic extreme polygenic risk score (PRS) for AD between cognitively healthy ε4 homozygotes aged ≥75 years (n = 213) and early-onset ε4 homozygote AD cases aged ≤65 years (n = 223) as an explanation for this diversity. Results: The PRS for AD was significantly higher in ε4 homozygote AD cases compared to older cognitively healthy ε4/ε4 controls (odds ratio [OR] 8.39; confidence interval [CI] 2.0-35.2; = .003). The difference in the same PRS …