Back
Full-text
Journal article

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

  • Demetrius LA Department of Organismic and Evolutionary Biology, Harvard University Cambridge, MA, USA ; Max Planck Institute for Molecular Genetics Berlin, Germany.
  • Magistretti PJ Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology Thuwal, Saudi Arabia ; Laboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne Lausanne, Switzerland.
  • Pellerin L Laboratory of Neuroenergetics, Department of Physiology, University of Lausanne Lausanne, Switzerland.
  • 2015-02-03
Published in:
  • Frontiers in physiology. - 2014
age-related disease
inverse cancer comorbidity
metabolic alteration
mitochondrial dysregulation
the Inverse Warburg effect
English 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.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/12972
Statistics
Document views: 2 File downloads:
  • fulltext.pdf: 0