Alzheimer’s disease: the Amyloid hypothesis and the Inverse Warburg effect

Frontiers in Physiology

卷:5

Pierre J Magistretti¹  Lloyd eDemetrius⁴  Luc ePellerin⁵ 

[1] Ecole Polytechnique Fédérale de Lausanne;

[2] Harvard University;

[3] King Abdullah University of Science and Technology;

[4] Max Planck Institute for Molecular Genetics;

[5] University of Lausanne;

关键词: age-related disease;    mitochondrial dysregulation;    metabolic alteration;    the Inverse Warburg effect;    inverse cancer comorbidity;   

DOI  :  10.3389/fphys.2014.00522

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown