ApoE2-Mediated Neuroprotection Against Alzheimer’s Disease: from Mechanism to Translation
type: CreativeWork
description: Alzheimer’s disease (AD) is the most common form of age-related dementia. Despite decades of research, the etiology and pathogenesis of AD are not well understood. Brain glucose hypometabolism has long been recognized as a prominent anomaly that occurs in the preclinical stage of AD. Recent studies suggest that glycolytic metabolism, the cytoplasmic pathway of the breakdown of glucose, may play a critical role in the development of AD. Glycolysis is essential for a variety of neural activities in the brain, including energy production, synaptic transmission, and redox homeostasis. Decreased glycolytic flux has been shown to correlate with the severity of amyloid and tau pathology in both preclinical and clinical AD patients. Moreover, increased glucose accumulation found in the brains of AD patients supports the hypothesis that glycolytic deficit may be a contributor to the development of this phenotype. In addition to AD, glycolic dysfunction has been observed in other neurodegenerative diseases, including Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis, strengthening the concept of glycolytic dysfunction as a common pathway leading to neurodegeneration. Humans possess three primary variants of the apolipoprotein E (ApoE) gene – ApoE*ԑ2, ApoE*ԑ3, and ApoE*ԑ4 – that confer differential susceptibility to AD. Recent findings indicate that neuronal glycolysis is significantly affected by human ApoE isoforms and glycolytic robustness may serve as a major mechanism that renders an ApoE2-bearing brain more resistant against the neurodegenerative risks for AD. In particular, these advances highlight a promising translational opportunity that involves targeting glycolysis to bolster brain metabolic resilience, and by such to alter the course of brain aging in fighting against the risks for not only AD but also other neurodegenerative diseases. In addition, AD has a multifactoral etiology, with age, sex, and ApoE genotype established as the top t…
abstract: Alzheimer’s disease (AD) is the most common form of age-related dementia. Despite decades of research, the etiology and pathogenesis of AD are not well understood. Brain glucose hypometabolism has long been recognized as a prominent anomaly that occurs in the preclinical stage of AD. Recent studies suggest that glycolytic metabolism, the cytoplasmic pathway of the breakdown of glucose, may play a critical role in the development of AD. Glycolysis is essential for a variety of neural activities in the brain, including energy production, synaptic transmission, and redox homeostasis. Decreased glycolytic flux has been shown to correlate with the severity of amyloid and tau pathology in both preclinical and clinical AD patients. Moreover, increased glucose accumulation found in the brains of AD patients supports the hypothesis that glycolytic deficit may be a contributor to the development of this phenotype. In addition to AD, glycolic dysfunction has been observed in other neurodegenerative diseases, including Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis, strengthening the concept of glycolytic dysfunction as a common pathway leading to neurodegeneration. Humans possess three primary variants of the apolipoprotein E (ApoE) gene – ApoE*ԑ2, ApoE*ԑ3, and ApoE*ԑ4 – that confer differential susceptibility to AD. Recent findings indicate that neuronal glycolysis is significantly affected by human ApoE isoforms and glycolytic robustness may serve as a major mechanism that renders an ApoE2-bearing brain more resistant against the neurodegenerative risks for AD. In particular, these advances highlight a promising translational opportunity that involves targeting glycolysis to bolster brain metabolic resilience, and by such to alter the course of brain aging in fighting against the risks for not only AD but also other neurodegenerative diseases. In addition, AD has a multifactoral etiology, with age, sex, and ApoE genotype established as the top t…
author: Zhang, Xin
language: en
keywords: Pharmacology, Neurosciences, Alzheimer's disease, apolipoprotein E, glycolysis, hexokinase, neuroprotection
date published: 2023-05-31
date modified: 2026-07-24T02:46:05Z
provider: University of Kansas
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Kansas

PropertyValue
property ID: Handle
value: https://hdl.handle.net/1808/37377