scholarly journals A Novel Approach to the Treatment and Prevention of Alzheimer’s Disease Based on the Pathology and Microbiology

2021 ◽  
pp. 1-7
Author(s):  
Herbert B. Allen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Current Treatment ◽  
Toll Like Receptor ◽  
Treatment And Prevention ◽  
Novel Approach ◽  
Periodic Administration ◽  
Toll Like Receptor 2 ◽  
Pass Through ◽  
The Brain

Utilizing the pathology and microbiology found in tissue from patients with documented Alzheimer’s disease (AD), the pathogenesis of this fateful disorder has been made clear. Borrelia burgdorferi and Treponema denticola spirochetes enter the brain, mostly via neuronal pathways and the entorhinal circulation. These organisms easily pass through the blood-brain barrier and have an affinity for neural tissue. Once in the brain, the spirochetes make intra- and extracellular biofilms, and it is the biofilms that create the pathology. Specifically, it is the intracellular biofilms that are ultimately responsible for neurofibrillary tangles and dendritic disintegration. The extracellular biofilms are responsible for the inflammation that initially is generated by the first responder, Toll-like receptor 2. The hypothesis that arises from this work is two-pronged: one is related to prevention; the other to treatment. Regarding prevention, it is very likely possible that AD could be prevented by periodic administration of penicillin (PCN), which would kill the spirochetes before they made biofilms; this would prevent the disease and would not allow any of the above deleterious changes generated by the biofilms to occur. As regards treatment, it may be possible to slow or prevent further decline in early AD by administration of PCN together with a biofilm disperser. The disperser would disrupt the biofilm coating and enable the PCN to kill the spirochetes. This protocol could be administered in a trial with the control arm utilizing the current treatment. The progress of the treatment could be evaluated by one of the current blood tests that is semi-quantitative. The specific protocols are listed.

scholarly journals Toll-Like Receptor 2 and NLRP3 Cooperate To Recognize a Functional Bacterial Amyloid, Curli

2014 ◽  
Vol 83 (2) ◽  
pp. 693-701 ◽  
Author(s):  
Glenn J. Rapsinski ◽  
Meghan A. Wynosky-Dolfi ◽  
Gertrude O. Oppong ◽  
Sarah A. Tursi ◽  
R. Paul Wilson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nlrp3 Inflammasome ◽  
Amyloid Β ◽  
Underlying Mechanism ◽  
Secondary Amyloidosis ◽  
Toll Like Receptor ◽  
Content Type ◽  
Caspase 1 ◽  
Toll Like Receptor 2

Amyloids are proteins with cross-β-sheet structure that contribute to pathology and inflammation in complex human diseases, including Alzheimer's disease, Parkinson's disease, type II diabetes, and secondary amyloidosis. Bacteria also produce amyloids as a component of their extracellular matrix during biofilm formation. Recently, several human amyloids were shown to activate the NLRP3 inflammasome, leading to the activation of caspase 1 and production of interleukin 1β (IL-1β). In this study, we investigated the activation of the NLRP3 inflammasome by bacterial amyloids using curli fibers, produced bySalmonella entericaserovar Typhimurium andEscherichia coli. Here, we show that curli fibers activate the NLRP3 inflammasome, leading to the production of IL-1β via caspase 1 activation. Investigation of the underlying mechanism revealed that activation of Toll-like receptor 2 (TLR2) by curli fibers is critical in the generation of IL-1β. Interestingly, activation of the NLRP3 inflammasome by curli fibers or by amyloid β of Alzheimer's disease does not cause cell death in macrophages. Overall, these data identify a cross talk between TLR2 and NLRP3 in response to the bacterial amyloid curli and generation of IL-1β as a product of this interaction.

scholarly journals Targeting Endothelin in Alzheimer’s Disease: A Promising Therapeutic Approach

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Shiwali Sharma ◽  
Tapan Behl ◽  
Anoop Kumar ◽  
Aayush Sehgal ◽  
Sukhbir Singh ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Outcome Data ◽  
Endothelin Receptors ◽  
Chemical Mediator ◽  
Promising Therapeutic Approach ◽  
Pass Through ◽  
The Brain ◽  
Conclusive Outcome

Endothelin is a chemical mediator that helps in maintaining balance within the blood-brain barrier by regulating the levels of toxicants and molecules which pass through the brain, suggesting that a rise in its production determines Alzheimer’s disease. The inequity in the amyloid β occurs due to a problem in its clearance from the brain initiating the production of reactive oxygen species and superoxide that activates a cascade wherein the release of inflammatory mediators and various enzymes like endothelin-converting enzymes take place. Furthermore, the cascade increases the levels of endothelin in the brain from endothelial cells. Endothelin levels are upregulated, which can be regulated by modulating the action of endothelin-converting enzymes and endothelin receptors. Hence, endothelin paves a pathway in the treatment of Alzheimer’s disease. In this article, we have covered various mechanisms and preclinical studies that support and direct endothelin involvement in the progression of Alzheimer’s disease by using various search tools such as PubMed, Science Direct, and Medline. Conclusive outcome data were extracted that all together defy contrivance pathways, potential drugs, endothelin receptors, and endothelin enzymes in our article giving profound importance to target endothelin for prevention and treatment of Alzheimer’s disease.

scholarly journals Disorders of cognitive activity in patients with multiple sclerosis and hepatocerebral degeneration and its prevention

2020 ◽  
Vol 24 (4) ◽  
pp. 589-594
Author(s):  
I. Voloshyn-Gaponov ◽  
I. Lantukh ◽  
P. Gaponov
Keyword(s):  
Multiple Sclerosis ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Functions ◽  
Verbal Memory ◽  
Cognitive Activity ◽  
Cognitive Disorders ◽  
Biological Aging ◽  
Treatment And Prevention ◽  
The Brain

Annotation. Currently, there is an increase in dementias of various origins, which is largely due to the tendency of the aging population of the globe, with adverse environmental factors. Dementia also occurs at a young, working-aged, which makes them not only a medical but also a social problem. The incidence of Alzheimer's disease (AD) is so high that the WHO has declared the 21st century the century of the AD epidemic. The task of the work is to conduct a comprehensive clinical and laboratory examination of patients with multiple sclerosis (MS) and patients with Wilson's disease (WD) to study the problem of neurodegenerative diseases. The Mini-Mental Status Exam (MMSE) scale was used to screen for cognitive function and to study the level of intellectual performance of patients. To determine verbal memory, the method was used: “memorization of 10 words”, and to study the personality and emotional sphere, the method of Derogatis SCl-90-P was used. The sample of patients with MS was 111 people, and psycho diagnostic examination of patients with WD was performed in 33 patients. Various cognitive disorders are characteristic of MS patients. The level of general intellectual productivity is in the range from normative indicators to very pronounced systemic disorders of cognitive functions. With the age of patients and the duration of the disease, the severity of these disorders increases. A comprehensive clinical and laboratory study showed that the pathogenesis and stages of development of the dementia process in patients with WD and MS coincide with those in patients with Alzheimer’s disease and depends on three groups of factors: genetic predisposition, natural (biological) aging, and endogenous and exogenous pathogenic factors. on the brain. The study concluded that in patients with WD and MS in the pathogenetic process are always involved structures that ensure the functioning of cognitive functions of the brain, which leads to the development of their defects. For the treatment and prevention of these patients, a comprehensive, pathogenetically grounded, and personalized therapy should be prescribed.

Alzheimer’s Disease and Parkinson’s Disease: A Review of Current Treatment Adopting a Nanotechnology Approach

2018 ◽  
Vol 24 (1) ◽  
pp. 22-45 ◽  
Author(s):  
Adriana Trompetero ◽  
Aldemar Gordillo ◽  
Mora Carolina del Pilar ◽  
Velasquillo María Cristina ◽  
Rosa Helena Bustos Cruz
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Side Effects ◽  
Systemic Circulation ◽  
Current Treatment ◽  
Parkinson’S Diseases ◽  
The Central Nervous System ◽  
Modifying Effect ◽  
Pass Through ◽  
Neuron Function

Neurodegenerative disorders (NDDs) are characterized by the progressive loss of structure or neuron function, often associated with neuronal death. Treatments for neurodegenerative diseases only address symptoms without having any disease-modifying effect but serious side effects. Currently, there is no effective treatment for NDDs. This is due to the poor flow of drugs to the blood-barrier brain (BBB) which does not allow macromolecules like proteins and peptides to pass through it. Targeted drug delivery to the central nervous system (CNS) for the diagnosis and treatment of NDDs, such as Alzheimer’s disease (AD), is restricted due to the limitations posed by the BBB as well as opsonization by plasma proteins in the systemic circulation and peripheral side-effects. Nanotechnology thereby presents a broad approach for transporting molecules through the BBB, thus allowing the entry of substances acting directly on the site affected by the disease. The aim of this review is to outline current strategies in nanotechnology for treating Alzheimer’s and Parkinson’s diseases.

No association of toll-like receptor 2 polymorphisms with Alzheimer's disease in Han Chinese

2011 ◽  
Vol 32 (10) ◽  
pp. 1924.e1-1924.e3 ◽  
Author(s):  
Jin-Tai Yu ◽  
Yan-Ping Sun ◽  
Jiang-Rong Ou ◽  
Wei-Zhen Cui ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Han Chinese ◽  
Toll Like Receptor ◽  
Toll Like Receptor 2

scholarly journals Pulmonary B cells ameliorate Alzheimer’s disease-like neuropathology

2020 ◽  
Author(s):  
Weixi Feng ◽  
Yanli Zhang ◽  
Tianqi Wang ◽  
Ze Wang ◽  
Yan Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
B Cells ◽  
B Cell ◽  
Memory Deficits ◽  
Brain Parenchyma ◽  
Toll Like Receptor ◽  
Amyloid Aβ ◽  
5Xfad Mice ◽  
The Brain

Increasing evidence shows that the peripheral immune system is involved in the pathogenesis of Alzheimer’s disease (AD). Here, we report that pulmonary B cells mitigate beta-Amyloid (Aβ) pathology in 5xFAD mice. The proportion of B cells rather than T cells increases in brain, meningeal and lung tissues in 3-month-old 5xFAD mice. Deletion of B cells aggravates Aβ load and memory deficits of 5xFAD mice. Mechanimsly, pulmonary B cells can migrate to the brain parenchyma and produce interleukin-35 that inhibits neuronal β-site APP-cleaving enzyme 1 expression, subsequently reducing the production of Aβ. In turn, proliferation of pulmonary B cells is associated with activation of toll-like receptor/nuclear factor kappa-B pathway by elevated Aβ that is drained from the brain parenchyma to the lungs via meningeal lymphatics. Furthermore, promoting pulmonary B cell proliferation via overexpression of B-cell-activating factor ameliorates brain Aβ load and improves cognitive functions of 10-month-old 5xFAD mice. Together, these results highlight the lungs as both immune targets and effector organs in Aβ pathogenesis. Pulmonary B cells might be a potential target against AD.

scholarly journals Differential Diagnosis of Alzheimer's Disease and Mild Cognitive Impairment Using the Structural and Diffusion MRI Features of the Brain

2021 ◽  
Author(s):  
Seyed Amir Zamanpour ◽  
Bahare Bigham ◽  
Mohamad-Hoseyn Sigari ◽  
Hoda Zare
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Diffusion Mri ◽  
Support Vector ◽  
Treatment And Prevention ◽  
Mri Features ◽  
The Brain ◽  
And Diffusion

Abstract Introduction: Accurate, fast, and reliable diagnosis of Alzheimer's Disease (AD) from Mild Cognitive Impairment (MCI) is crucial for prescribing proper treatment and prevention of disease progression. At first glance, structural and diffusion MRI images, are affected by neurodegenerative proceedings in AD and MCI. In this study, we are looking for the most effective features to detect and differentiate between healthy normal control (NC), AD, and MCI groups by non-invasive Magnetic Resonance Imaging (MRI) method and propose the automatic multi-class classification using the structural and diffusion MRI Features of the brain. Methods: The structural and diffusion MRI data were downloaded from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database on three groups including AD, MCI, and NC subjects. Four famous classification models of machine learning were used to discover the best classification as a diagnostic tool for separation of the NC, AD and MCI groups. Results: Taken together, our results from this study lead to classify three groups for differentiation between the NC group and patients with MCI and AD, with average accuracy factor 89.9% for Support Vector Machine (SVM) and 91.9% for Artificial Neural Network (ANN) using selected features. Conclusions: Top 9 regions repetitive of WM based on four types of features are the caudate nucleus, corpus callosum, hippocampus, para hippocampus, temporal gyrus, putamen nucleus, cingulate gyrus, the region of 36 and 3 Brodmann. Therefore, these regions could be considered for identifying, monitoring, and future drug trials that could target this brain region to AD and MCI Management.

Triggering microglia through toll-like receptor 2 pathway induced interferon β expression in cell and animal model of Alzheimer’s disease

Neuroreport ◽  
2018 ◽  
Vol 29 (17) ◽  
pp. 1456-1462 ◽  
Author(s):  
Nooshin Heshmati-Fakhr ◽  
Fattah Sotoodehnejadnematalahi ◽  
Niloufar Yousefi ◽  
Mohammad Sayyah ◽  
Sayed Masoud Hosseini ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Model ◽  
Toll Like Receptor ◽  
Interferon Β ◽  
Model Of Alzheimer’S Disease ◽  
Toll Like Receptor 2
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