Locus Coeruleus Dysfunction and Trigeminal Mesencephalic Nucleus Degeneration: A Cue for Periodontal Infection Mediated Damage in Alzheimer’s Disease?

Flavio Pisani (), Valerio Pisani, Francesca Arcangeli, Alice Harding and Sim K. Singhrao
Additional contact information
Flavio Pisani: Programme Lead, MSc/MClinDent in Clinical Periodontology, Faculty of Clinical and Biomedical Sciences, School of Dentistry, University of Central Lancashire, Preston PR1 2HE, UK
Valerio Pisani: I.R.C.C.S. “Santa Lucia” Foundation, Neurology and Neurorehabilitation Unit, Via Ardeatina, 306, 00179 Rome, Italy
Francesca Arcangeli: Azienda Sanitaria Locale ASLRM1, Nuovo Regina Margherita Hospital, Geriatric Department-Advanced Centre for Dementia and Cognitive Disorders, Via Emilio Morosini, 30, 00153 Rome, Italy
Alice Harding: Dementia and Neurodegenerative Disease Research Group, Faculty of Clinical and Biomedical Sciences, School of Dentistry, University of Central Lancashire, Preston PR1 2HE, UK
Sim K. Singhrao: Dementia and Neurodegenerative Disease Research Group, Faculty of Clinical and Biomedical Sciences, School of Dentistry, University of Central Lancashire, Preston PR1 2HE, UK

IJERPH, 2023, vol. 20, issue 2, 1-14

Abstract: Alzheimer’s disease (AD) is a leading neurodegenerative disease with deteriorating cognition as its main clinical sign. In addition to the clinical history, it is characterized by the presence of two neuropathological hallmark lesions; amyloid-beta (Aβ) and neurofibrillary tangles (NFTs), identified in the brain at post-mortem in specific anatomical areas. Recently, it was discovered that NFTs occur initially in the subcortical nuclei, such as the locus coeruleus in the pons, and are said to spread from there to the cerebral cortices and the hippocampus. This contrasts with the prior acceptance of their neuropathology in the enthorinal cortex and the hippocampus. The Braak staging system places the accumulation of phosphorylated tau (p-tau) binding to NFTs in the locus coeruleus and other subcortical nuclei to precede stages I–IV. The locus coeruleus plays diverse psychological and physiological roles within the human body including rapid eye movement sleep disorder, schizophrenia, anxiety, and depression, regulation of sleep-wake cycles, attention, memory, mood, and behavior, which correlates with AD clinical behavior. In addition, the locus coeruleus regulates cardiovascular, respiratory, and gastrointestinal activities, which have only recently been associated with AD by modern day research enabling the wider understanding of AD development via comorbidities and microbial dysbiosis. The focus of this narrative review is to explore the modes of neurodegeneration taking place in the locus coeruleus during the natural aging process of the trigeminal nerve connections from the teeth and microbial dysbiosis, and to postulate a pathogenetic mechanism due to periodontal damage and/or infection focused on Treponema denticola .

Keywords: locus coeruleus; mesencephalic trigeminal nucleus; trigeminal nerve; neurodegeneration; Alzheimer’s disease; periodontal disease; Treponema denticola (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

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