scholarly journals Dysbiosis in Alzheimer’s Disease Might be Triggered by Certain Classes of Antibiotics with Time-lapse: New Insights in the Pathogenesis?

2022 ◽  
Author(s):  
Gábor Ternák ◽  
Márton Németh ◽  
Martin Rozanovic ◽  
Lajos Bogár
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Broad Spectrum ◽  
Memory Loss ◽  
Time Lapse ◽  
Antibiotic Consumption ◽  
European Countries ◽  
Main Hypothesis ◽  
Positive Correlation

Background and objectives: Alzheimer's disease (AD) is a progressive neurodegenerative illness, responsible for 60-70% of all dementias, affecting over 50 million people worldwide, and nearly 11 million in European countries. Several putative factors are identified in the literature as causative agents or risk factors for the development of AD. The amyloid cascade hypothesis has been the main hypothesis about the pathophysiology of AD for decades. Recent studies raised the possible role of dysbiosis in the development of AD which prevents memory loss. The amyloid-β (Aβ) deposition might be considered as an inflammatory reaction to certain molecular products arising from the altered microbiome. Based on the above observations, it has been suspected, that antibiotic consumption patterns of different antibiotic classes might be associated with the prevalence of AD in European countries. Methods: Antibiotic consumption (ECDC) for 1997-2007, 2008-2018, and as the whole 1997-2018 period, have been compared to the AD prevalence for 2018 expressed in percentage of the population and statistically analyzed by Pearson calculation. Results: A significant positive correlation has been found between the AD prevalence (2018) and the average quinolone consumption for the year 1997-2007 (p: 0.044). A similar association was not observed for the entire 22 years (1997-2018) of the average quinolone consumption, and the years 2008-18, indicating 10-20 years of time-lapse between the antibiotic exposure and the development of AD. The ratio of broad-spectrum and narrow-spectrum antibiotics (B/N) estimated in the ECDC database for the years of 2008-2018 showed a strong positive association with AD prevalence (2018) (p: 0.026) and a positive correlation tendency for the entire 22 years 1997-2018 (p: 0.063), but none for the years 1997-2007 (p: 0.241). Broad-spectrum, beta-lactamase sensitive penicillin (J01CA) consumption showed a positive (non-significant) correlation with the prevalence of AD for the years 2008-2018 (p:0.080).Discussion: Our study indicated the possible sequential role of certain classes of antibiotics in the development of dysbiosis leading to amyloid deposits of AD, which strengthen the possible role of different mediator molecules (short-chain fatty acids, lipopolysaccharides, etc.) produced by the altered microbiome in the development of AD.

scholarly journals Isovitexin modulates autophagy in Alzheimer’s disease via miR-107 signalling

2020 ◽  
Vol 11 (1) ◽  
pp. 391-401
Author(s):  
Jiang Cheng ◽  
Guowei Wang ◽  
Na Zhang ◽  
Fang Li ◽  
Lina Shi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Loss ◽  
The Elderly ◽  
Tnf Α ◽  
Autophagic Process ◽  
Molecular Signals ◽  
Ad Mouse Model ◽  
Mtor Signalling

AbstractBackground:Alzheimer’s disease (AD) is an ultimately fatal, degenerative brain disease in the elderly people. In the current work, we assessed the defensive capability of isovitexin (IVX) through an intracerebroventricular injection of streptozotocin (STZ)-induced AD mouse model.Methods:Mice were separated into four cohorts: sham-operated control mice; STZ-intoxicated Alzheimer’s mice; IVX cohort, IVX + STZ; and Ant-107 cohort, antagomiR-107 + IVX/STZ as in the IVX cohort.Results:The outcomes indicated that IVX administration ameliorated spatial memory loss and blunted a cascade of neuro-noxious episodes – including increased amyloid-beta (Aβ) and degraded myelin basic protein burden, neuroinflammation (represented by elevated caspase-1, TNF-α and IL-6 levels) and autophagic dysfunction (represented by altered LC3-II, Atg7 and beclin-1 expressions) – via the inhibition of PI3K/Akt/mTOR signalling axis. We considered the question of whether the epigenetic role of microRNA-107 (miR-107) has any impact on these events, by using antagomiR-107.Conclusion:This probing underscored that miR-107 could be a pivotal regulatory button in the activation of molecular signals linked with the beneficial autophagic process and anti-inflammatory activities in relation to IVX treatment. Hence, this report exemplifies that IVX could guard against Aβ toxicity and serve as an effectual treatment for patients afflicted with AD.

scholarly journals Getting to NO Alzheimer’s Disease: Neuroprotection versus Neurotoxicity Mediated by Nitric Oxide

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Rachelle Balez ◽  
Lezanne Ooi
Keyword(s):  
Nitric Oxide ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathways ◽  
Neuronal Excitability ◽  
Neurodegenerative Disorder ◽  
Memory Loss ◽  
Protective Role ◽  
Ionic Mechanisms

Alzheimer’s disease (AD) is a neurodegenerative disorder involving the loss of neurons in the brain which leads to progressive memory loss and behavioral changes. To date, there are only limited medications for AD and no known cure. Nitric oxide (NO) has long been considered part of the neurotoxic insult caused by neuroinflammation in the Alzheimer’s brain. However, focusing on early developments, prior to the appearance of cognitive symptoms, is changing that perception. This has highlighted a compensatory, neuroprotective role for NO that protects synapses by increasing neuronal excitability. A potential mechanism for augmentation of excitability by NO is via modulation of voltage-gated potassium channel activity (Kv7 and Kv2). Identification of the ionic mechanisms and signaling pathways that mediate this protection is an important next step for the field. Harnessing the protective role of NO and related signaling pathways could provide a therapeutic avenue that prevents synapse loss early in disease.

scholarly journals Herpesvirus infections and immunological disturbances in patients with different stages of Alzheimer’s disease

2021 ◽  
Vol 66 (2) ◽  
pp. 129-139
Author(s):  
S. A. Krynskiy ◽  
I. K. Malashenkova ◽  
D. P. Ogurtsov ◽  
N. A. Khailov ◽  
E. I. Chekulaeva ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Clinical Stage ◽  
Memory Loss ◽  
Control Group ◽  
Immunological Parameters ◽  
Humoral And Cellular Immunity

Introduction. Alzheimer’s disease (AD) is a multifactorial disease that leads to a progressive memory loss, visualspatial impairments, emotional and personality changes. As its earliest pre-dementia clinical stage, amnestic mild cognitive impairment syndrome (aMCI) is currently considered. Neuroinflammation plays a role in the development and progression of aMCI and the initial stage of AD, which can be supported by immunological disorders of a systemic character. Study of factors, including infections, influencing immune disorders and systemic inflammatory response in patients with aMCI, is of great importance.The aim of this study was to obtain new data on the possible role of herpesvirus infections in the development and progression of aMCI.Material and methods. 100 patients with aMCI diagnosis, 45 patients with AD, 40 people from the control group were enrolled into the study. The frequency of DNA detection of herpesviruses (Epstein–Barr virus (EBV), human herpesviruses (HHV) type 6 and 7, cytomegalovirus (CMV)), the levels of viral load and the serological markers of herpesvirus infections (IgG to HHV-1, IgG to CMV) were determined. Immunological studies included an assessment of the level of the main pro-inflammatory and anti-inflammatory cytokines, and indicators of humoral and cellular immunity.Results. The study found an increased detection rate of EBV in saliva and a higher level of EBV DNA in saliva in aMCI and AD than in the control group. A relationship between the presence of active EBV infection and changes in immunological parameters in patients with aMCI were found. It was also discovered that the level of IgG antibodies to CMV is associated with the stage of AD.Discussion. The results indicate a possible role of EBV- and CMV-induced infections in the development of immunological changes which are typical for mild cognitive impairment and in the progression of AD. Conclusion. The obtained data can be important for prognostic methods addressing AD development, including its pre-dementia stage, and for new approaches to individualized treatment and prevention.

scholarly journals ROLE OF MITOCHONDRIAL DISFUNCTION IN THE DEVELOPMENT OF ALZHEIMER’S DISEASE

2021 ◽  
Vol 67 (1) ◽  
pp. 57-66
Author(s):  
V.V. Ganzha ◽  
◽  
E.A. Lukyanetz ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Tau Protein ◽  
Mitochondrial Dynamics ◽  
Memory Loss ◽  
Disease Process ◽  
Hyperphosphorylated Tau Protein ◽  
Amyloid Aβ

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory loss and multiple cognitive impairments. Several decades of intensive research have shown that multicellular changes are involved in AD’s development and progression, including mitochondrial damage, synaptic dysfunction, formation and accumulation of beta-amyloid (Aβ), formation and accumulation of hyperphosphorylated tau protein, and loss of neurons in patients with this disease. Among them, mitochondrial dysfunction and synaptic damage are the primary manifestations in the disease process. Recent studies have also shown that defective mitophagy caused by Aβ and tau protein are the main indicators in AD’s pathogenesis. This review includes an overview of recent researches on the role of mitochondria in AD development. The review summarizes several aspects of mitochondrial dysfunction, including abnormal mitochondrial dynamics, changes in mitochondrial DNA, and calcium dyshomeostasis in AD pathogenesis

scholarly journals Neuroprotective Herbs for the Management of Alzheimer’s Disease

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 543
Author(s):  
Julie Gregory ◽  
Yasaswi V. Vengalasetti ◽  
Dale E. Bredesen ◽  
Rammohan V. Rao
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Medicinal Plants ◽  
Disease Progression ◽  
Memory Loss ◽  
Herbal Remedies ◽  
Alternative Interventions ◽  
Drug Candidates ◽  
Personality Changes

Background—Alzheimer’s disease (AD) is a multifactorial, progressive, neurodegenerative disease that is characterized by memory loss, personality changes, and a decline in cognitive function. While the exact cause of AD is still unclear, recent studies point to lifestyle, diet, environmental, and genetic factors as contributors to disease progression. The pharmaceutical approaches developed to date do not alter disease progression. More than two hundred promising drug candidates have failed clinical trials in the past decade, suggesting that the disease and its causes may be highly complex. Medicinal plants and herbal remedies are now gaining more interest as complementary and alternative interventions and are a valuable source for developing drug candidates for AD. Indeed, several scientific studies have described the use of various medicinal plants and their principal phytochemicals for the treatment of AD. This article reviews a subset of herbs for their anti-inflammatory, antioxidant, and cognitive-enhancing effects. Methods—This article systematically reviews recent studies that have investigated the role of neuroprotective herbs and their bioactive compounds for dementia associated with Alzheimer’s disease and pre-Alzheimer’s disease. PubMed Central, Scopus, and Google Scholar databases of articles were collected, and abstracts were reviewed for relevance to the subject matter. Conclusions—Medicinal plants have great potential as part of an overall program in the prevention and treatment of cognitive decline associated with AD. It is hoped that these medicinal plants can be used in drug discovery programs for identifying safe and efficacious small molecules for AD.

scholarly journals Possible Role of STIM1 Sensor Signal in Memory Loss Connected with Familial Alzheimer's Disease

2015 ◽  
Vol 108 (2) ◽  
pp. 588a
Author(s):  
Maria Ryazantseva ◽  
Ksenia Skobeleva ◽  
Anna Goncharova ◽  
Nikolai Kamyshev ◽  
Elena Kaznacheyeva
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Loss ◽  
Sensor Signal ◽  
Familial Alzheimer’S Disease ◽  
Familial Alzheimer's Disease

scholarly journals The Therapeutic and Diagnostic Potential of Amyloid β Oligomers Selective Antibodies to Treat Alzheimer’s Disease

2022 ◽  
Vol 15 ◽  
Author(s):  
Kirsten L. Viola ◽  
Maira A. Bicca ◽  
Adrian M. Bebenek ◽  
Daniel L. Kranz ◽  
Vikas Nandwana ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Loss ◽  
Amyloid Β ◽  
Intraventricular Injection ◽  
Wild Type ◽  
Memory Dysfunction ◽  
Imaging Methods ◽  
5Xfad Mice

Improvements have been made in the diagnosis of Alzheimer’s disease (AD), manifesting mostly in the development of in vivo imaging methods that allow for the detection of pathological changes in AD by magnetic resonance imaging (MRI) and positron emission tomography (PET) scans. Many of these imaging methods, however, use agents that probe amyloid fibrils and plaques–species that do not correlate well with disease progression and are not present at the earliest stages of the disease. Amyloid β oligomers (AβOs), rather, are now widely accepted as the Aβ species most germane to AD onset and progression. Here we report evidence further supporting the role of AβOs as pathological instigators of AD and introduce promising anti-AβO diagnostic probes capable of distinguishing the 5xFAD mouse model from wild type mice by PET and MRI. In a developmental study, Aβ oligomers in 5xFAD mice were found to appear at 3 months of age, just prior to the onset of memory dysfunction, and spread as memory worsened. The increase of AβOs is prominent in the subiculum and correlates with concomitant development of reactive astrocytosis. The impact of these AβOs on memory is in harmony with findings that intraventricular injection of synthetic AβOs into wild type mice induced hippocampal dependent memory dysfunction within 24 h. Compelling support for the conclusion that endogenous AβOs cause memory loss was found in experiments showing that intranasal inoculation of AβO-selective antibodies into 5xFAD mice completely restored memory function, measured 30–40 days post-inoculation. These antibodies, which were modified to give MRI and PET imaging probes, were able to distinguish 5xFAD mice from wild type littermates. These results provide strong support for the role of AβOs in instigating memory loss and salient AD neuropathology, and they demonstrate that AβO selective antibodies have potential both for therapeutics and for diagnostics.

scholarly journals Inflammatory and Infectious Processes Serve as Links between Atrial Fibrillation and Alzheimer’s Disease

2020 ◽  
Vol 21 (9) ◽  
pp. 3226 ◽  
Author(s):  
Gabriela Lopes Martins ◽  
Rita Carolina Figueiredo Duarte ◽  
Marat Alexandrovich Mukhamedyarov ◽  
András Palotás ◽  
Cláudia Natália Ferreira ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Memory Loss ◽  
Predictive Biomarkers ◽  
Infectious Agents ◽  
Increased Risk ◽  
Inflammatory Processes

Atrial fibrillation (AF) is one of the most prevalent forms of arrhythmia that carries an increased risk of stroke which, in turn, is strongly associated with cognitive decline. The majority of dementia cases are caused by Alzheimer’s disease (AD) with obscure pathogenesis. While the exact mechanisms are unknown, the role of inflammatory processes and infectious agents have recently been implicated in both AD and AF, suggesting a common link between these maladies. Here, we present the main shared pathways underlying arrhythmia and memory loss. The overlapping predictive biomarkers and emerging joint pharmacological approaches are also discussed.

scholarly journals Genomics: New Light on Alzheimer’s Disease Research

2018 ◽  
Vol 19 (12) ◽  
pp. 3771 ◽  
Author(s):  
Yeong Jung ◽  
Yoon Kim ◽  
Mridula Bhalla ◽  
Sung Lee ◽  
Jinsoo Seo
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Association Studies ◽  
Memory Loss ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
And Behavior ◽  
Generation Sequencing

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that represents a major cause of death in many countries. AD is characterized by profound memory loss, disruptions in thinking and reasoning, and changes in personality and behavior followed by malfunctions in various bodily systems. Although AD was first identified over 100 years ago, and tremendous efforts have been made to cure the disease, the precise mechanisms underlying the onset of AD remain unclear. The recent development of next-generation sequencing tools and bioinformatics has enabled us to investigate the role of genetics in the pathogenesis of AD. In this review, we discuss novel discoveries in this area, including the results of genome-wide association studies (GWAS) that have implicated a number of novel genes as risk factors, as well as the identification of epigenetic regulators strongly associated with the onset and progression of AD. We also review how genetic risk factors may interact with age-associated, progressive decreases in cognitive function in patients with AD.

scholarly journals THE ROLE OF BETA-AMYLOID IN NORM AND AT ALZHEIMER`S DISEASE

2020 ◽  
Vol 66 (6) ◽  
pp. 88-96
Author(s):  
Yu. N. Tyshchenko ◽  
◽  
E.A. Lukyanetz ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Plaques ◽  
Memory Loss ◽  
Physiological Role ◽  
Neuronal Loss ◽  
The Brain ◽  
Progressive Cognitive Impairment ◽  
Existing Data

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment and memory loss. The pathogenesis of AD is complex, depends on many factors, and has not yet been fully studied. Extracellular deposits of amyloid-beta (Ab) peptide in the form of senile plaques, the formation of intracellular neurofibrillary tangles, and massive neuronal loss are considered as the main pathological signs of AD. However, recently there have been many data that indicate other pathways involved in the pathogenesis of AD. This review aims to analyze the existing data on the physiological role of Ab in the brain under normal conditions and its pathological role in Alzheimer’s disease.

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