Pathogenesis of Alzheimer's disease : Multiple interacting causes against which amyloid precursor protein protects

Shah, A.F. and Morris, J.A. and Wray, M. (2020) Pathogenesis of Alzheimer's disease : Multiple interacting causes against which amyloid precursor protein protects. Medical Hypotheses, 143: 110035. ISSN 0306-9877

Abstract

Alzheimer's disease is the commonest form of senile dementia. It is characterised by neuronal cell death and amyloid deposition. Amyloid precursor protein (APP), which is highly conserved in evolution, is expressed in neurones in response to a wide range of damaging agents. The hypothesis proposed is that APP has a protective function to counter damage but if it fails and the neurone dies then breakdown products of APP miss-fold and lead to amyloid deposition. This fits with the evidence that amyloid deposition is a consequence rather than a cause of cell death. Germ line mutations in APP impair the protective role and lead to increased neuronal loss in response to damage. This leads to early onset and severe Alzheimer's disease. Inflammation, infection, hypoxia, trauma and pollution are damaging agents which interact to cause the disease. The bacteria which cause chronic periodontitis appear to have a significant role. Prevention needs to focus on avoiding trauma, reducing pollution and improving dental hygiene. Furthermore we should attempt to optimise the oral microbial flora by suppressing the growth of pathogenic bacteria that cause gum disease and the bacterial pathogens in the oropharynx that cause life threatening infections following viral upper respiratory infections. This leads to a key research question: does the regular consumption of natural live yoghurt reduce the carriage of periodontal and oropharyngeal bacterial pathogens? Theoretical considerations indicate it should and if so regular natural live yoghurt consumption could be an important preventive agent. © 2020 The Authors