Title |
Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect
|
---|---|
Published in |
Frontiers in Physiology, January 2015
|
DOI | 10.3389/fphys.2014.00522 |
Pubmed ID | |
Authors |
Lloyd A. Demetrius, Pierre J. Magistretti, Luc Pellerin |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 29% |
Korea, Democratic People's Republic of | 1 | 14% |
India | 1 | 14% |
Switzerland | 1 | 14% |
Unknown | 2 | 29% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 5 | 71% |
Practitioners (doctors, other healthcare professionals) | 1 | 14% |
Scientists | 1 | 14% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 3 | 1% |
United Kingdom | 2 | <1% |
Greece | 1 | <1% |
Unknown | 287 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 57 | 19% |
Researcher | 49 | 17% |
Student > Master | 42 | 14% |
Student > Bachelor | 37 | 13% |
Student > Postgraduate | 13 | 4% |
Other | 45 | 15% |
Unknown | 50 | 17% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 58 | 20% |
Biochemistry, Genetics and Molecular Biology | 54 | 18% |
Neuroscience | 47 | 16% |
Medicine and Dentistry | 25 | 9% |
Engineering | 11 | 4% |
Other | 39 | 13% |
Unknown | 59 | 20% |