Periodontal dysbiosis associates with reduced CSF Aβ42 in cognitively normal elderly

Kamer, Angela R.; Pushalkar, Smruti; Gulivindala, Deepthi; Butler, Tracy; Li, Yang; Annam, Kumar Raghava Chowdary; Glodzik, Lidia; Ballman, Karla V.; Corby, Patricia; Blennow, Kaj; Zetterberg, Henrik; Saxena, Deepak; Leon, Mony J. de

doi:10.1002/dad2.12172

Cited by 30 publications

(35 citation statements)

References 45 publications

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“…However, the theory of oral focal infection has not received enough attention and theoretical support. With the advances of microbiome research, the association between oral microbes and a variety of human chronic diseases has been studied, including inflammatory bowel disease, 3 cancers, 4 cardiovascular diseases, 5 Alzheimer’s disease, 6 diabetes, 7 rheumatoid arthritis, 8 and preterm birth 9 (Fig. 1 ).…”

Section: Introductionmentioning

confidence: 99%

Oral microbiota in human systematic diseases

et al. 2022

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Oral bacteria directly affect the disease status of dental caries and periodontal diseases. The dynamic oral microbiota cooperates with the host to reflect the information and status of immunity and metabolism through two-way communication along the oral cavity and the systemic organs. The oral cavity is one of the most important interaction windows between the human body and the environment. The microenvironment at different sites in the oral cavity has different microbial compositions and is regulated by complex signaling, hosts, and external environmental factors. These processes may affect or reflect human health because certain health states seem to be related to the composition of oral bacteria, and the destruction of the microbial community is related to systemic diseases. In this review, we discussed emerging and exciting evidence of complex and important connections between the oral microbes and multiple human systemic diseases, and the possible contribution of the oral microorganisms to systemic diseases. This review aims to enhance the interest to oral microbes on the whole human body, and also improve clinician’s understanding of the role of oral microbes in systemic diseases. Microbial research in dentistry potentially enhances our knowledge of the pathogenic mechanisms of oral diseases, and at the same time, continuous advances in this frontier field may lead to a tangible impact on human health.

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Section: Introductionmentioning

confidence: 99%

Oral microbiota in human systematic diseases

et al. 2022

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“…The inflammatory/ dysbiotic environment may facilitate bacterial access to the subarachnoid space through the cribriform plate. Periodontal research also suggests that oral bacteria or inflammatory biproducts can access the brain via both blood and neuronal routes (Riviere et al, 2002) and our studies suggest oral bacteria can induce amyloid pathology (Riviere et al, 2002;Kamer et al, 2015Kamer et al, , 2021. As such, bacterial DNA whose sources could be from the gut and respiratory pathways or proinflammatory cytokines may access the brain via an olfactory route at the nose-brain interface.…”

Section: Nose-brain Interface: Immunologymentioning

confidence: 65%

The Brain-Nose Interface: A Potential Cerebrospinal Fluid Clearance Site in Humans

Mehta

Sherbansky²,

Kamer³

et al. 2022

Front. Physiol.

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The human brain functions at the center of a network of systems aimed at providing a structural and immunological layer of protection. The cerebrospinal fluid (CSF) maintains a physiological homeostasis that is of paramount importance to proper neurological activity. CSF is largely produced in the choroid plexus where it is continuous with the brain extracellular fluid and circulates through the ventricles. CSF movement through the central nervous system has been extensively explored. Across numerous animal species, the involvement of various drainage pathways in CSF, including arachnoid granulations, cranial nerves, perivascular pathways, and meningeal lymphatics, has been studied. Among these, there is a proposed CSF clearance route spanning the olfactory nerve and exiting the brain at the cribriform plate and entering lymphatics. While this pathway has been demonstrated in multiple animal species, evidence of a similar CSF egress mechanism involving the nasal cavity in humans remains poorly consolidated. This review will synthesize contemporary evidence surrounding CSF clearance at the nose-brain interface, examining across species this anatomical pathway, and its possible significance to human neurodegenerative disease. Our discussion of a bidirectional nasal pathway includes examination of the immune surveillance in the olfactory region protecting the brain. Overall, we expect that an expanded discussion of the brain-nose pathway and interactions with the environment will contribute to an improved understanding of neurodegenerative and infectious diseases, and potentially to novel prevention and treatment considerations.

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“…Low levels of sLF may assist oral dysbiosis, which, in turn, may produce long-term infections and a pro-inflammatory response that weakens the blood brain barrier, facilitating colonization of brain tissue by periodontal bacteria [ 61 ] and accelerating neuroinflammation that contribute to AD pathology [ 62 ]. In this vein, previous studies have shown an association between periodontal disease and brain Aβ accumulation in normal aging, suggesting that periodontal inflammation/infection may accelerate brain Aβ deposition [ 63 , 64 ]. Our results complement these findings, suggesting that reductions of sLF relate to increased regional Aβ burden, which may reflect early immunological alterations potentially associated with higher risk of developing AD [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Salivary lactoferrin is associated with cortical amyloid-beta load, cortical integrity, and memory in aging

et al. 2021

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Background Aging is associated with declining protective immunity and persistent low-grade inflammatory responses, which significantly contribute to Alzheimer’s disease (AD) pathogenesis. Detecting aging-related cerebral vulnerability associated with deterioration of the immune system requires from non-invasive biomarkers able to detect failures in the brain-immunity connection. Reduced levels of salivary lactoferrin (sLF), an iron-binding protein with immunomodulatory activity, have been related to AD diagnosis. However, it remains unknown whether decreased sLF is associated with increased cortical amyloid-beta (Aβ) load and/or with loss of cortical integrity in normal aging. Methods Seventy-four cognitively normal older adults (51 females) participated in the study. We applied multiple linear regression analyses to assess (i) whether sLF is associated with cortical Aβ load measured by 18F-Florbetaben (FBB)-positron emission tomography (PET), (ii) whether sLF-related variations in cortical thickness and cortical glucose metabolism depend on global Aβ burden, and (iii) whether such sLF-related cortical abnormalities moderate the relationship between sLF and cognition. Results sLF was negatively associated with Aβ load in parieto-temporal regions. Moreover, sLF was related to thickening of the middle temporal cortex, increased FDG uptake in the posterior cingulate cortex, and poorer memory. These associations were stronger in individuals showing the highest Aβ burden. Conclusions sLF levels are sensitive to variations in cortical Aβ load, structural and metabolic cortical abnormalities, and subclinical memory impairment in asymptomatic older adults. These findings provide support for the use of sLF as a non-invasive biomarker of cerebral vulnerability in the general aging population.

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Periodontal dysbiosis associates with reduced CSF Aβ42 in cognitively normal elderly

Cited by 30 publications

References 45 publications

Oral microbiota in human systematic diseases

Oral microbiota in human systematic diseases

The Brain-Nose Interface: A Potential Cerebrospinal Fluid Clearance Site in Humans

Salivary lactoferrin is associated with cortical amyloid-beta load, cortical integrity, and memory in aging

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