Alzheimer’s as a metabolic disease
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Empirical evidence indicates that impaired mitochondrial energy metabolism is the defining characteristic of almost all cases of Alzheimer’s disease (AD). Evidence is reviewed supporting the general hypothesis that the up-regulation of OxPhos activity, a metabolic response to mitochondrial dysregulation, drives the cascade of events leading to AD. This mode of metabolic alteration, called the Inverse Warburg effect, is postulated as an essential compensatory mechanism of energy production to maintain the viability of impaired neuronal cells. This article appeals to the inverse comorbidity of cancer and AD to show that the amyloid hypothesis, a genetic and neuron-centric model of the origin of sporadic forms of AD, is not consistent with epidemiological data concerning the age-incidence rates of AD. A view of Alzheimer’s as a metabolic disease—a condition consistent with mitochondrial dysregulation and the Inverse Warburg effect, will entail a radically new approach to diagnostic and therapeutic strategies.
KeywordsInverse Warburg effect Amyloid cascade hypothesis Oxidative phosphorylation Glycolysis Aging
Support from the Max Planck Institute for Molecular Genetics, Berlin, Germany, is gratefully acknowledged.
Conflict of interest
The authors declare that they have no conflict of interest.
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