Article
Version 1
Preserved in Portico This version is not peer-reviewed
Metabolic and Hormonal Contributors to Neuronal Necrosis in Alzheimer’s Dementia
Version 1
: Received: 22 May 2018 / Approved: 24 May 2018 / Online: 24 May 2018 (05:59:26 CEST)
Version 2 : Received: 3 June 2018 / Approved: 4 June 2018 / Online: 4 June 2018 (13:16:46 CEST)
Version 2 : Received: 3 June 2018 / Approved: 4 June 2018 / Online: 4 June 2018 (13:16:46 CEST)
How to cite: Overholt, M. Metabolic and Hormonal Contributors to Neuronal Necrosis in Alzheimer’s Dementia. Preprints 2018, 2018050335. https://doi.org/10.20944/preprints201805.0335.v1 Overholt, M. Metabolic and Hormonal Contributors to Neuronal Necrosis in Alzheimer’s Dementia. Preprints 2018, 2018050335. https://doi.org/10.20944/preprints201805.0335.v1
Abstract
Research into the causes of neurotoxicity in Alzheimer’s Dementia (AD) has focused on neurofibrillary tangles and beta amyloid (Aβ) plaques. This paper proposes the heterodox theory that these hallmarks of AD are the visible effects, not direct causes of neuronal necrosis. Rather AD results from a combination of age-induced, disproportional decline in physiological support for aerobic metabolism, and dysregulation of the sleep cycle processes. The hypothesis is that the decimation of neurons in AD results from a combination of neurotoxicity and increased apoptosis caused by: 1. direct damage from toxic waste products of anaerobic glycolysis due to a progressive decline in the capacity of neurons to perform oxidative phosphorylation (OXPHOS) and an increased reliance on anaerobic glycolysis to meet metabolic needs; 2. impaired cellular repair and effluent release due to dysregulation of non-rapid eye movement (NREM) sleep allowing damage to cell membranes and synaptic junctions to accumulate inducing a chronic inflammatory response; 3. indirect damage from products produced by inflammatory reaction to toxic metabolites; 4. neuronal apoptosis from the AβPP-mediated pathway due to the age-induced decline of growth hormone (GH), GH-releasing hormone (GHRH) and insulin-like growth factor (IGF).
Keywords
Alzheimer’s Dementia; anaerobic neurotoxicity; inflammation; neuronal apoptosis; Non-REM Sleep
Subject
Biology and Life Sciences, Neuroscience and Neurology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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