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Full-Text Articles in Medicine and Health Sciences
Cerebral Lactate Metabolism And Memory: Implications For Alzheimer's Disease, Richard Andrew Harris
Cerebral Lactate Metabolism And Memory: Implications For Alzheimer's Disease, Richard Andrew Harris
Electronic Thesis and Dissertation Repository
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by amyloid plaques that are comprised of aggregated amyloid-beta peptides. These toxic proteins promote mitochondrial dysfunction and neuronal cell death. A shift in metabolism away from oxidative phosphorylation and toward aerobic glycolysis, with the concomitant production of lactate, affords neurons a survival advantage against amyloid-beta toxicity. Recent evidence now suggests that aerobic glycolysis in the brain plays a critical role in supporting synaptic plasticity, learning, and memory. However, the role of aerobic glycolysis and lactate metabolism in AD-mediated cognitive decline is unknown. My objective was to test the hypotheses that aerobic glycolysis …
Amyloid Beta Resistance And The Warburg Effect: Re-Examining Alzheimer's Disease, Jordan Taylor Newington
Amyloid Beta Resistance And The Warburg Effect: Re-Examining Alzheimer's Disease, Jordan Taylor Newington
Electronic Thesis and Dissertation Repository
Alzheimer’s disease (AD) is characterized by deposition of the amyloid beta (Ab) peptide in the brain, an event which frequently but not universally correlates with nerve cell death. Although most nerve cells die in response to Ab, small populations of cells are able to survive by becoming resistant to Ab toxicity. Understanding the mechanisms by which cells become resistant to Ab may reveal novel treatments for AD. Interestingly, nerve cell lines selected for resistance against Ab exhibit increased glucose uptake and glycolytic flux. Here I show that these metabolic changes are mediated through an upregulation of pyruvate dehydrogenase kinase 1 …