Impact of Genetic Risk Factors for Alzheimer's Disease on Brain Glucose Metabolism

Mol Neurobiol. 2021 Jun;58(6):2608-2619. doi: 10.1007/s12035-021-02297-x. Epub 2021 Jan 21.

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.

Keywords: Alzheimer’s disease; Genetic risk factors; Glucose metabolism; Glycolysis; Mitochondrial respiration.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism*
  • Animals
  • Brain / metabolism*
  • Genetic Predisposition to Disease*
  • Glucose / metabolism*
  • Glycolysis / genetics
  • Humans
  • Risk Factors

Substances

  • Glucose