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dc.contributor.authorDemetrius, Lloyd A.
dc.contributor.authorMagistretti, Pierre J.
dc.contributor.authorPellerin, Luc
dc.date.accessioned2015-01-28T13:34:50Z
dc.date.available2015-01-28T13:34:50Z
dc.date.issued2015-01-14
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.2014.00522
dc.identifier.issn1664-042X
dc.identifier.pmid25642192
dc.identifier.doi10.3389/fphys.2014.00522
dc.identifier.urihttp://hdl.handle.net/10754/338984
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.
dc.language.isoen
dc.publisherFrontiers Media SA
dc.relation.urlhttp://www.frontiersin.org/Systems_Biology/10.3389/fphys.2014.00522/abstract
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.
dc.subjectage-related disease
dc.subjectmitochondrial dysregulation
dc.subjectmetabolic alteration
dc.subjectthe Inverse Warburg effect
dc.subjectinverse cancer comorbidity
dc.titleAlzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Program
dc.identifier.journalFrontiers in Physiology
dc.identifier.pmcidPMC4294122
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionDepartment of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA
dc.contributor.institutionMax Planck Institute for Molecular Genetics, Berlin, Germany
dc.contributor.institutionLaboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
dc.contributor.institutionLaboratory of Neuroenergetics, Department of Physiology, University of Lausanne, Lausanne, Switzerland
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)
kaust.personMagistretti, Pierre J.
refterms.dateFOA2018-06-13T16:08:51Z


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