scholarly journals Can Porphyromonas gingivalis Contribute to Alzheimer’s Disease Already at the Stage of Gingivitis?

2021 ◽  
pp. 1-5
Author(s):  
Ingar Olsen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Porphyromonas Gingivalis ◽  
Blood Stream ◽  
Brain Inflammation ◽  
Periodontal Pathogens ◽  
M1 Phase ◽  
Supragingival Plaque ◽  
The Brain

Alzheimer’s disease (AD) has been associated with periodontitis, which starts as gingivitis. Similar to periodontitis, gingivitis bacteria, bacterial products, and inflammatory mediators can travel to the brain via the blood stream and promote brain inflammation. Periodontal pathogens such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, both associated with AD, have been found in dental plaque of children already at the age of 3. It is suggested that these bacteria during long-term exposure may drive microglia (brain resident macrophage cells) into a pro-inflammatory M1 phase where they contribute to AD rather than protect against it. This notion comes from studies in mice showing that microglia actually can “remember” previous inflammatory challenge and become “trained” or “tolerant” to toxins like lipopolysaccharide. If gingivitis has an impact on AD, which should be verified, AD prophylaxis should start already at this pre-periodontitis stage with removal of supragingival plaque.

scholarly journals Recovery of Dementia Syndrome following Treatment of Brain Inflammation

2020 ◽  
Vol 10 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Jong-hoon Lee ◽  
Su-hee Choi ◽  
Chul Joong Lee ◽  
Sang-suk Oh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Cell ◽  
Brain Inflammation ◽  
Japanese Study ◽  
Long Period ◽  
Dementia Syndrome ◽  
Leprosy Patients ◽  
The Brain

Aim/Background: This research aims to prevent progression from mild cognitive impairment (MCI) to Alzheimer’s disease. A Japanese study of leprosy patients revealed that the incidence of dementia in leprosy patients was lower than that in patients taking dapsone who had never been treated. But a similar study the following year refuted the finding of less dementia in leprosy patients taking dapsone. According to conflicting reports, Mycobacterium leprae was a factor in reducing the incidence of Alzheimer’s disease. Thus, we formed a hypothesis that if dapsone is administered to patients without leprosy but with MCI and the prophylactic effect of dementia syndrome is observed over a long period of time, we can determine whether dapsone can prevent the progression of MCI to dementia syndrome. If dementia does not occur after treating inflammation in brain cells while dementia develops after a certain long-term period (usually within 2–3 years), brain cell inflammation can be demonstrated as the cause of dementia. Methods: This is a prospective cohort research. We report on an elderly patient diagnosed with MCI from February 2008 to January 2019. The patient took dapsone 100 mg once a day from 2010 to 2015 for the treatment of MCI. Since 2016, the production of dapsone has ceased in Korea. In June 2018, the patient was diagnosed with Alzheimer’s disease. The patient took Aricept for the treatment of Alzheimer’s disease but complained of serious side effects. And dapsone was re-administered to the patient from November 2018. Results: The patient recovered to MCI and improved her daily life owing to the treatment with dapsone. The drug controls the inflammatory response in the brain, irrespective of whether proteins are deposited in neurons. Conclusions:This finding means that dementia syndrome is an inflammatory disease. This research suggests that diagnostic criteria for Alzheimer’s disease should be based on the presence or absence of inflammation in neurons. Because inflammation in neurons can occur in middle age due to various causes, we can treat inflammation in neurons and prevent and treat dementia syndrome, including Alzheimer’s disease.

Integrated Biomarkers for Depression in Alzheimer’s Disease: A Critical Review

2017 ◽  
Vol 14 (4) ◽  
pp. 441-452 ◽  
Author(s):  
Sofia Wenzler ◽  
Christian Knochel ◽  
Ceylan Balaban ◽  
Dominik Kraft ◽  
Juliane Kopf ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Affect Regulation ◽  
Current Evidence ◽  
Diagnostic Process ◽  
Neuropsychiatric Manifestation ◽  
The Brain ◽  
Control Functional

Depression is a common neuropsychiatric manifestation among Alzheimer’s disease (AD) patients. It may compromise everyday activities and lead to a faster cognitive decline as well as worse quality of life. The identification of promising biomarkers may therefore help to timely initiate and improve the treatment of preclinical and clinical states of AD, and to improve the long-term functional outcome. In this narrative review, we report studies that investigated biomarkers for AD-related depression. Genetic findings state AD-related depression as a rather complex, multifactorial trait with relevant environmental and inherited contributors. However, one specific set of genes, the brain derived neurotrophic factor (BDNF), specifically the Val66Met polymorphism, may play a crucial role in AD-related depression. Regarding neuroimaging markers, the most promising findings reveal structural impairments in the cortico-subcortical networks that are related to affect regulation and reward / aversion control. Functional imaging studies reveal abnormalities in predominantly frontal and temporal regions. Furthermore, CSF based biomarkers are seen as potentially promising for the diagnostic process showing abnormalities in metabolic pathways that contribute to AD-related depression. However, there is a need for standardization of methodological issues and for replication of current evidence with larger cohorts and prospective studies.

NF-κB as a Key Mediator of Brain Inflammation in Alzheimer’s Disease

2019 ◽  
Vol 18 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Chul Ju Hwang ◽  
Dong-Young Choi ◽  
Mi Hee Park ◽  
Jin Tae Hong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treatment Strategies ◽  
Close Correlation ◽  
Specific Protein ◽  
Brain Inflammation ◽  
Cytokines And Chemokines ◽  
Inflammatory Drugs ◽  
Peptide Fibrils

Alzheimer’s disease is the most common form of dementia. It is characterized by betaamyloid peptide fibrils which are extracellular deposition of a specific protein, accompanied by extensive neuroinflammation. Various studies show the presence of a number of inflammation markers in the AD brain: elevated inflammatory cytokines and chemokines, and an accumulation of activated microglia in the damaged regions. NF-κB is a family of redox sensitive transcriptional factors, and it is known that NF-κB has binding sites in the promoter region of the genes involved in amyloidogenesis and inflammation. Long-term use of non-steroidal anti-inflammatory drugs prevents progression of AD and delays its onset, suggesting that there is a close correlation between NF-κB and AD pathogenesis. This study aims to (1) assess the association between NF-κB activity and AD through discussion of a variety of experimental and clinical studies on AD and (2) review treatment strategies designed to treat or prevent AD with NF-κB inhibitors.

scholarly journals Influencia del estrés en la Enfermedad de Alzheimer. // Stress influence in Alzheimer’s disease

Ciencia Unemi ◽  
2018 ◽  
Vol 10 (25) ◽  
pp. 123
Author(s):  
Maria Alejandra Vallejo-Johnson ◽  
Patricia Marcial-Velastegui
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Damage ◽  
The Body ◽  
Daily Routine ◽  
Stressful Situation ◽  
The Individual ◽  
Stress Influences ◽  
The Brain

Existen diversos estudios que proponen las causas de la Enfermedad de Alzheimer (EA), las cuales pueden ser: biológicas, genéticas, cronológicas y ambientales, dentro de ésta última se encuentra el estrés como una influencia para el inicio de dicha patología. Según las distintas teorías del estrés, el sujeto, al encontrarse frente a una situación estresante, sufre diversos cambios en su cuerpo para sobrellevar dicho acontecimiento. El cerebro es el encargado de poner al cuerpo en alerta y en marcha para actuar frente a dicho cambio. El estrés prolongado conlleva a alteraciones en las vías cerebrales, específicamente un daño neuronal del hipocampo, el cual es el encargado de los recuerdos y memoria. Éste al verse afectado, repercute en la memoria del sujeto y por lo tanto empieza a fallar; el sujeto se ve en la incapacidad para recordar y realizar distintas actividades rutinarias. Mediante la investigación documental y encuestas a profesionales de la salud, se obtuvo información tanto del estrés como de la Enfermedad de Alzheimer para luego concluir en la influencia del mismo en el origen de la enfermedad. Se concluye que el estrés perenne repercute en la muerte de neuronas del hipocampo lo que conlleva a la EA. AbstractThere are different studies that propose that the causes of Alzheimer might be biological, genetic, chronological and environmental. Within the environmental aspects, the stress influences the beginning of this pathology. There are several studies that propose the causes of Alzheimer's disease (AD), which can be: biological, genetic, chronological and environmental, within the latter is the stress that influences the beginning of this pathology. According to different theories of stress, the individual, while facing a stressful situation, experiences many changes in the body in order to deal with this situation. The brain is in charge of alerting the body to protect itself against that change. The long-term stress alters the brain pathways, producing specifically a neuronal damage in the hippocampus that is responsible for memories and memory. This affects memory and therefore individual begins to fail, and then, the person cannot remember how to do the daily routine. Through bibliographical research and surveys applied to healthcare professionals, information was obtained on both stress and Alzheimer's disease to establish the influence of that condition on the disease. The study concludes that long-term stress affects the death of neurons in the hippocampus, which leads to AD.

scholarly journals Porphyromonas gingivalis Outer Membrane Vesicles as the Major Driver of and Explanation for Neuropathogenesis, the Cholinergic Hypothesis, Iron Dyshomeostasis, and Salivary Lactoferrin in Alzheimer’s Disease

2021 ◽  
pp. 1-34
Author(s):  
Peter L. Nara ◽  
Daniel Sindelar ◽  
Marc S. Penn ◽  
Jan Potempa ◽  
W. Sue T. Griffin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Outer Membrane ◽  
Porphyromonas Gingivalis ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Direct Role ◽  
Cholinergic Hypothesis ◽  
Genetic Mechanisms ◽  
The Brain

Porphyromonas gingivalis (Pg) is a primary oral pathogen in the widespread biofilm-induced “chronic” multi-systems inflammatory disease(s) including Alzheimer’s disease (AD). It is possibly the only second identified unique example of a biological extremophile in the human body. Having a better understanding of the key microbiological and genetic mechanisms of its pathogenesis and disease induction are central to its future diagnosis, treatment, and possible prevention. The published literature around the role of Pg in AD highlights the bacteria’s direct role within the brain to cause disease. The available evidence, although somewhat adopted, does not fully support this as the major process. There are alternative pathogenic/virulence features associated with Pg that have been overlooked and may better explain the pathogenic processes found in the “infection hypothesis” of AD. A better explanation is offered here for the discrepancy in the relatively low amounts of “Pg bacteria” residing in the brain compared to the rather florid amounts and broad distribution of one or more of its major bacterial protein toxins. Related to this, the “Gingipains Hypothesis”, AD-related iron dyshomeostasis, and the early reduced salivary lactoferrin, along with the resurrection of the Cholinergic Hypothesis may now be integrated into one working model. The current paper suggests the highly evolved and developed Type IX secretory cargo system of Pg producing outer membrane vesicles may better explain the observed diseases. Thus it is hoped this paper can provide a unifying model for the sporadic form of AD and guide the direction of research, treatment, and possible prevention.

scholarly journals Porphyromonas Gingivalis May Seek the Alzheimer’s Disease Brain to Acquire Iron from Its Surplus

2021 ◽  
Vol 5 (1) ◽  
pp. 79-86
Author(s):  
Ingar Olsen
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Free Radicals ◽  
Porphyromonas Gingivalis ◽  
Amyloid Β ◽  
Iron Chelators ◽  
Brain Areas ◽  
Beneficial Effects ◽  
The Brain

Iron accumulates in the brain of subjects with Alzheimer’s disease (AD). Here it promotes the aggregation of amyloid-β plaques in which it is abundant. Iron induces amyloid-β neurotoxicity by damaging free radicals and causing oxidative stress in brain areas with neurodegeneration. It can also bind to tau in AD and enhance the toxicity of tau through co-localization with neurofibrillary tangles and induce accumulation of these tangles. Porphyromonas gingivalis is a key oral pathogen in the widespread biofilm-induced disease “chronic” periodontitis, and recently, has been suggested to have an important role in the pathogenesis of AD. P. gingivalis has an obligate requirement for iron. The current paper suggests that P. gingivalis seeks the AD brain, where it has been identified, to satisfy this need. If this is correct, iron chelators binding iron could have beneficial effects in the treatment of AD. Indeed, studies from both animal AD models and humans with AD have indicated that iron chelators, e.g., lactoferrin, can have such effects. Lactoferrin can also inhibit P. gingivalis growth and proteinases and its ability to form biofilm.

Emphasizing roles of BDNF promoters and inducers in Alzheimer's disease for improving impaired cognition and memory

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Madhuparna Banerjee ◽  
Rekha R. Shenoy
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurotrophic Factor ◽  
Molecular Mechanisms ◽  
Signal Transduction Pathway ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Low Levels ◽  
The Brain

Abstract Brain-derived neurotrophic factor (BDNF) is a crucial neurotrophic factor adding to neurons’ development and endurance. The amount of BDNF present in the brain determines susceptibility to various neurodegenerative diseases. In Alzheimer’s disease (AD), often it is seen that low levels of BDNF are present, which primarily contributes to cognition deficit by regulating long-term potentiation (LTP) and synaptic plasticity. Molecular mechanisms underlying the synthesis, storage and release of BDNF are widely studied. New molecules are found, which contribute to the signal transduction pathway. Two important receptors of BDNF are TrkB and p75NTR. When BDNF binds to the TrkB receptor, it activates three main signalling pathways-phospholipase C, MAPK/ERK, PI3/AKT. BDNF holds an imperative part in LTP and dendritic development, which are essential for memory formation. BDNF supports synaptic integrity by influencing LTP and LTD. This action is conducted by modulating the glutamate receptors; AMPA and NMDA. This review paper discusses the aforesaid points along with inducers of BDNF. Drugs and herbals promote neuroprotection by increasing the hippocampus’ BDNF level in various disease-induced animal models for neurodegeneration. Advancement in finding pertinent molecules contributing to the BDNF signalling pathway has been discussed, along with the areas that require further research and study.

scholarly journals Alternative Treatment for Alzheimer’s Disease: Porphyromonas gingivalis Inhibitors

2019 ◽  
pp. 23-25
Author(s):  
Pouriya Sadeghighazichaki
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Porphyromonas Gingivalis ◽  
Virulence Factor ◽  
Bacterial Load ◽  
Amyloid Plaque ◽  
Plaque Deposition ◽  
The Brain

Porphyromonas gingivalis (P. gingivalis), has been identified as a primary pathogen in causing chronic periodontitis, or gum inflammation. P. gingivalis was also isolated in brain samples of patients suffering from Alzheimer’s disease. A virulence factor of P. gingivalis called gingipains, releases proteases responsible for neurodegeneration and has been identified in the brain of patients suffering from Alzheimer’s. Studies show that mice infected with P. gingivalis demonstrate an increase in amyloid plaque deposition in brain samples. Further investigation identified gingipains as a neurotoxic agent, both in vivo and in vitro, which impacts the structure of tau protein, responsible for the normal functioning of neurons. Small-molecule inhibitors targeting gingipains are utilized to prevent the neurotoxic effects of gingipains and facilitate neuronal regeneration. Inhibition of this virulence factor reduced the overall bacterial load, blocked amyloid-beta production, prevented neuroinflammation, and allowed for neuronal recovery. These findings provide a new outlook for the onset of Alzheimer’s disease and elucidate a much-needed potential treatment for the condition.

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