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...

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Bibliographic Details
Published in:Frontiers in physiology 2015-01, Vol.5, p.522-522
Main Authors: Demetrius, Lloyd A, Magistretti, Pierre J, Pellerin, Luc
Format: Article
Language:English
Subjects:
age-related disease
inverse cancer comorbidity
metabolic alteration
mitochondrial dysregulation
Physiology
the Inverse Warburg effect
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Summary: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.
ISSN:1664-042X
1664-042X
DOI:10.3389/fphys.2014.00522