Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Permanent link to this recordhttp://hdl.handle.net/10754/338984
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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.
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
PublisherFrontiers Media SA
JournalFrontiers in Physiology
PubMed Central IDPMC4294122
The following license files are associated with this item:
- Alzheimer's as a metabolic disease.
- Authors: Demetrius LA, Driver J
- Issue date: 2013 Dec
- The inverse association of cancer and Alzheimer's: a bioenergetic mechanism.
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- Issue date: 2013 May 6
- Preventing Alzheimer's disease by means of natural selection.
- Authors: Demetrius LA, Driver JA
- Issue date: 2015 Jan 6
- Sex differences in Alzheimer's disease: metabolic reprogramming and therapeutic intervention.
- Authors: Demetrius LA, Eckert A, Grimm A
- Issue date: 2021 Dec
- Mitochondrial dysfunction: the missing link between aging and sporadic Alzheimer's disease.
- Authors: Grimm A, Friedland K, Eckert A
- Issue date: 2016 Apr