Alzheimer's disease alters oligodendrocytic glycolytic and ketolytic gene expression
This study shows that Alzheimer's disease (AD) is strongly correlated with impaired brain glucose metabolism.

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
March 2021

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.

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