Alzheimer's disease alters oligodendrocytic glycolytic and ketolytic gene expression

Erin R. Saito, Justin B. Miller, Oscar Harari, Carlos Cruchaga, Kathie A. Mihindukulasuriya, John S.K. Kauwe, Benjamin T. Bikman

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Introduction: Sporadic Alzheimer's disease (AD) is strongly correlated with impaired brain glucose metabolism, which may affect AD onset and progression. Ketolysis has been suggested as an alternative pathway to fuel the brain. Methods: RNA-seq profiles of post mortem AD brains were used to determine whether dysfunctional AD brain metabolism can be determined by impairments in glycolytic and ketolytic gene expression. Data were obtained from the Knight Alzheimer's Disease Research Center (62 cases; 13 controls), Mount Sinai Brain Bank (110 cases; 44 controls), and the Mayo Clinic Brain Bank (80 cases; 76 controls), and were normalized to cell type: astrocytes, microglia, neurons, oligodendrocytes. Results: In oligodendrocytes, both glycolytic and ketolytic pathways were significantly impaired in AD brains. Ketolytic gene expression was not significantly altered in neurons, astrocytes, and microglia. Discussion: Oligodendrocytes may contribute to brain hypometabolism observed in AD. These results are suggestive of a potential link between hypometabolism and dysmyelination in disease physiology. Additionally, ketones may be therapeutic in AD due to their ability to fuel neurons despite impaired glycolytic metabolism.

Original languageEnglish
Pages (from-to)1474-1486
Number of pages13
JournalAlzheimer's and Dementia
Volume17
Issue number9
DOIs
StatePublished - Sep 2021

Bibliographical note

Publisher Copyright:
© 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association

Keywords

  • Alzheimer's disease
  • astrocytes
  • glycolysis
  • ketolysis
  • metabolic RNA-seq profiles
  • microglia
  • neurons
  • oligodendrocytes

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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