Global Energy Metabolism Deficit in Alzheimer Disease Brain - 21/11/24

Doi : 10.14283/jpad.2023.91

Viharkumar Patel ^1,^⁎ , J. Mill ², O.C. Okonkwo ³, S. Salamat ^5,⁶, L. Li ^2,⁴, T. Raife ⁵

¹ Department of Pathology and Laboratory Medicine, University of California-Davis, 4400 V Street Suite 1114, 95817, Sacramento, CA, USA

² Department of Chemistry, University of Wisconsin-Madison, 53706, Madison, WI, USA

³ Clinical Science Center, Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, 53792, Madison, WI, USA

⁴ School of Pharmacy, University of Wisconsin-Madison, 53705, Madison, WI, USA

⁵ Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, 53705, Madison, WI, USA

⁶ Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, 53705, Madison, WI, USA

^a vppatel@ucdavis.edu vppatel@ucdavis.edu

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Abstract

Background

The understanding of Alzheimer’s disease (AD) has been dominated by the amyloid hypothesis. However, therapies targeting beta-amyloid have largely failed, generating interest in other potential pathogenic factors including energy metabolism.

Objectives

To interrogate canonical energy metabolism pathways from human prefrontal cortical tissue samples obtained from necropsy comparing AD and control.

Design, Setting, and Participants

Postmortem pre-frontal cortical tissue from 10 subjects histologically diagnosed with AD and 10 control (CTRL) subjects was subjected to untargeted metabolomics to interrogate energy metabolism pathways. The samples were matched by age, sex, and postmortem interval.

Metabolite Measurements

Untargeted metabolomics analyses were via Metabolon®.

Results

Glucose-derived energy metabolites in the glycolytic and pentose phosphate pathway and the ketone body β-hydroxybutyrate were uniformly decreased in AD brain vs. CTRL brain.

Conclusion

This pilot study aimed to identify energy metabolism abnormalities using untargeted brain metabolomics in two independent subject cohorts. Our study revealed a pattern of global energy deficit in AD brain, supporting a growing body of evidence of deficient energy metabolism in AD.

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Key words : Alzheimer disease, metabolomics, energy metabolism deficits, ketone body, beta-hydroxybutyrate

Plan

Introduction

Methods

Participants brain samples and subject demographics

Materials and reagents, sample preparation, and liquid chromatography/mass spectrometry (LC/MS) parameters

These authors contributed equally to this manuscript.

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Vol 11 - N° 1

P. 171-178 - janvier 2024 Retour au numéro

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Global Energy Metabolism Deficit in Alzheimer Disease Brain - 21/11/24

Abstract

Background

Objectives

Design, Setting, and Participants

Metabolite Measurements

Results

Conclusion

Plan

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