Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect

Handle URI:
http://hdl.handle.net/10754/338984
Title:
Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect
Authors:
Demetrius, Lloyd A.; Magistretti, Pierre J. ( 0000-0002-6678-320X ) ; Pellerin, Luc
Abstract:
Epidemiological and biochemical studies show that the sporadic forms of Alzheimer's disease (AD) are characterized by the following hallmarks: (a) An exponential increase with age; (b) Selective neuronal vulnerability; (c) Inverse cancer comorbidity. The present article appeals to these hallmarks to evaluate and contrast two competing models of AD: the amyloid hypothesis (a neuron-centric mechanism) and the Inverse Warburg hypothesis (a neuron-astrocytic mechanism). We show that these three hallmarks of AD conflict with the amyloid hypothesis, but are consistent with the Inverse Warburg hypothesis, a bioenergetic model which postulates that AD is the result of a cascade of three events—mitochondrial dysregulation, metabolic reprogramming (the Inverse Warburg effect), and natural selection. We also provide an explanation for the failures of the clinical trials based on amyloid immunization, and we propose a new class of therapeutic strategies consistent with the neuroenergetic selection model.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Citation:
Demetrius LA, Magistretti PJ and Pellerin L (2015) Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect. Front. Physiol. 5:522. doi: 10.3389/fphys.2014.00522
Publisher:
Frontiers Media SA
Journal:
Frontiers in Physiology
Issue Date:
14-Jan-2015
DOI:
10.3389/fphys.2014.00522
PubMed ID:
25642192
PubMed Central ID:
PMC4294122
Type:
Article
ISSN:
1664-042X
Additional Links:
http://www.frontiersin.org/Systems_Biology/10.3389/fphys.2014.00522/abstract
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorDemetrius, Lloyd A.en
dc.contributor.authorMagistretti, Pierre J.en
dc.contributor.authorPellerin, Lucen
dc.date.accessioned2015-01-28T13:34:50Z-
dc.date.available2015-01-28T13:34:50Z-
dc.date.issued2015-01-14en
dc.identifier.citationDemetrius LA, Magistretti PJ and Pellerin L (2015) Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect. Front. Physiol. 5:522. doi: 10.3389/fphys.2014.00522en
dc.identifier.issn1664-042Xen
dc.identifier.pmid25642192en
dc.identifier.doi10.3389/fphys.2014.00522en
dc.identifier.urihttp://hdl.handle.net/10754/338984en
dc.description.abstractEpidemiological and biochemical studies show that the sporadic forms of Alzheimer's disease (AD) are characterized by the following hallmarks: (a) An exponential increase with age; (b) Selective neuronal vulnerability; (c) Inverse cancer comorbidity. The present article appeals to these hallmarks to evaluate and contrast two competing models of AD: the amyloid hypothesis (a neuron-centric mechanism) and the Inverse Warburg hypothesis (a neuron-astrocytic mechanism). We show that these three hallmarks of AD conflict with the amyloid hypothesis, but are consistent with the Inverse Warburg hypothesis, a bioenergetic model which postulates that AD is the result of a cascade of three events—mitochondrial dysregulation, metabolic reprogramming (the Inverse Warburg effect), and natural selection. We also provide an explanation for the failures of the clinical trials based on amyloid immunization, and we propose a new class of therapeutic strategies consistent with the neuroenergetic selection model.en
dc.language.isoenen
dc.publisherFrontiers Media SAen
dc.relation.urlhttp://www.frontiersin.org/Systems_Biology/10.3389/fphys.2014.00522/abstracten
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en
dc.subjectage-related diseaseen
dc.subjectmitochondrial dysregulationen
dc.subjectmetabolic alterationen
dc.subjectthe Inverse Warburg effecten
dc.subjectinverse cancer comorbidityen
dc.titleAlzheimer's disease: the amyloid hypothesis and the Inverse Warburg effecten
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalFrontiers in Physiologyen
dc.identifier.pmcidPMC4294122en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionDepartment of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USAen
dc.contributor.institutionMax Planck Institute for Molecular Genetics, Berlin, Germanyen
dc.contributor.institutionLaboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerlanden
dc.contributor.institutionLaboratory of Neuroenergetics, Department of Physiology, University of Lausanne, Lausanne, Switzerlanden
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorMagistretti, Pierre J.en

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