Human ApoE Isoforms Differentially Modulate Brain Glucose and Ketone Body Metabolism: Implications for Alzheimer's Disease Risk Reduction and Early Intervention.
https://www.ncbi.nlm.nih.gov/pubmed/29967007
SIGNIFICANCE STATEMENT
We uncovered hexokinase as a key cytosolic point in the glucose metabolism that is differentially modulated by the three ApoE genotypes. The differences in hexokinase expression and activity exhibited in the three ApoE brains may underlie their distinct impact on brain glucose utilization and further susceptibility to AD. Therefore, a therapeutic approach that could circumvent the deficiencies in the cytosolic metabolism of glucose by providing glucose metabolizing intermediates, e.g., pyruvate, may hold benefits for ApoE4 carriers, who are at high risk for AD. The bioenergetic robustness may translate into enhanced synaptic activity and, ultimately, reduces the risk of developing AD and/or delays the onset of clinical manifestation.