Impact of Genetic Risk Factors for Alzheimer’s Disease on Brain Glucose Metabolism
Abstract
Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects more than 30 million people worldwide. Despite growing knowledge of AD pathophysiology, a complete understanding of the pathogenic mechanisms underpinning AD is lacking, and there is currently no cure for AD. Extant literature suggests that AD is a polygenic and multifactorial disease underscored by complex and dynamic pathogenic mechanisms. Despite extensive research and clinical trials, there has been a dearth of novel drugs for AD treatment on the market since memantine in 2003. This lack of therapeutic success has directed the entire research community to approach the disease from a different angle. In this review, we discuss growing evidence for the close link between altered glucose metabolism and AD pathogenesis by exploring how genetic risk factors for AD are associated with dysfunctional glucose metabolism. We also discuss modification of genes responsible for metabolic pathways implicated in AD pathology.
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Altered brain metabolism, especially increased aerobic glycolysis and impaired oxygen consumption in the brains of ApoE4 carriers, is suggested by studies from human plasma and humanized mouse models.
“Altered brain metabolism, especially increased aerobic glycolysis and impaired oxygen consumption in the brains of ApoE4 carriers, is suggested in studies from human plasma and humanized mouse models.2”
From ApoE4-dependent lysosomal cholesterol accumulation impairs mitochondrial homeostasis and oxidative phosphorylation in human astrocytes (2023) · cites this paper as [3]
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Self-citation
- Authors
- Cho, S., Lee, H., & Seo, J.
- Affiliations
- Daegu Gyeongbuk Institute of Science and Technology (KR)
- Corresponding author
- Seo, Jinsoo
- Venue
- Molecular Neurobiology
- Published
- 2021-01-21
- Volume
- 58
- Issue
- 6
- Pages
- 2608-2619
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- OpenAlex
- W3122321909
- Cited by
- 25
- References
- 19
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 3 · 2023: 8 · 2022: 3 · 2021: 2
- FWCI
- 0.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Science ICT and Future Planning (2018M3C7A1056275, 2019R1C1C1008591)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, genetic risk factors, brain glucose metabolism, polygenic disease, metabolic pathways, AD pathogenesis, neurodegeneration, therapeutic drug development
- MeSH terms
- Alzheimer Disease, Animals, Brain, Glucose, Glycolysis, Humans, Risk Factors, Genetic Predisposition to Disease
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