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Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect
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 hallmar...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294122/ https://www.ncbi.nlm.nih.gov/pubmed/25642192 http://dx.doi.org/10.3389/fphys.2014.00522 |
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author | Demetrius, Lloyd A. Magistretti, Pierre J. Pellerin, Luc |
author_facet | Demetrius, Lloyd A. Magistretti, Pierre J. Pellerin, Luc |
author_sort | Demetrius, Lloyd A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4294122 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-42941222015-01-30 Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect Demetrius, Lloyd A. Magistretti, Pierre J. Pellerin, Luc Front Physiol Physiology 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. Frontiers Media S.A. 2015-01-14 /pmc/articles/PMC4294122/ /pubmed/25642192 http://dx.doi.org/10.3389/fphys.2014.00522 Text en Copyright © 2015 Demetrius, Magistretti and Pellerin. http://creativecommons.org/licenses/by/4.0/ This 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. |
spellingShingle | Physiology Demetrius, Lloyd A. Magistretti, Pierre J. Pellerin, Luc Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect |
title | Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect |
title_full | Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect |
title_fullStr | Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect |
title_full_unstemmed | Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect |
title_short | Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect |
title_sort | alzheimer's disease: the amyloid hypothesis and the inverse warburg effect |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294122/ https://www.ncbi.nlm.nih.gov/pubmed/25642192 http://dx.doi.org/10.3389/fphys.2014.00522 |
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