Final published version
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Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Pathogenesis of Alzheimer's disease
T2 - Multiple interacting causes against which amyloid precursor protein protects
AU - Shah, A.F.
AU - Morris, J.A.
AU - Wray, M.
PY - 2020/10/10
Y1 - 2020/10/10
N2 - 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
AB - 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
KW - Alzheimer's disease
KW - Amyloid precursor protein
KW - Chronic periodontitis
KW - Magnetite particulates
KW - Systemic inflammation
KW - Trauma
KW - Yoghurt
U2 - 10.1016/j.mehy.2020.110035
DO - 10.1016/j.mehy.2020.110035
M3 - Journal article
VL - 143
JO - Medical Hypotheses
JF - Medical Hypotheses
SN - 0306-9877
M1 - 110035
ER -