APOE and metabolic dysfunction in Alzheimer's disease

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

13 Scopus citations


The strongest genetic risk factor for sporadic Alzheimer's disease (AD) is carriage of the E4 allele of APOE. Metabolic dysfunction also increases risk of dementia and AD. Facing a need for effective therapies and an aging global population, studies aimed at uncovering new therapeutic targets for AD have become critical. Insight into the biology underlying the effects of E4 and metabolic impairment on the brain may lead to novel therapies to reduce AD risk. An understudied hallmark of both AD patients and E4 individuals is a common metabolic impairment—cerebral glucose hypometabolism. This is a robust and replicated finding in humans, and begins decades prior to cognitive decline. Possession of E4 also appears to alter several other aspects of cerebral glucose metabolism, fatty acid metabolism, and management of oxidative stress through the pentose phosphate pathway. A critical knowledge gap in AD is the mechanism by which APOE alters cerebral metabolism and clarification as to its relevance to AD risk. Facing a need for effective therapies, studies aimed at uncovering new therapeutic targets have become critical. One such approach is to gain a better understanding of the metabolic mechanisms that may underlie E4-associated cognitive dysfunction and AD risk.

Original languageEnglish
Title of host publicationMetabolic and Bioenergetic Drivers of Neurodegenerative Disease
Subtitle of host publicationNeurodegenerative Disease Research and Commonalities with Metabolic Diseases
EditorsGrażyna Söderbom, Russell Esterline, Jan Oscarsson, Mark P. Mattson
Number of pages21
StatePublished - 2020

Publication series

NameInternational Review of Neurobiology
ISSN (Print)0074-7742
ISSN (Electronic)2162-5514

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Inc.


  • APOE
  • Alzheimer's disease
  • Metabolism

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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