Alpha1-chimaerin, a Rac1 GTPase-activating protein, is expressed at reduced mRNA levels in the brain of Alzheimer’s disease patients

Understanding the mechanisms involved in cognitive resilience in Alzheimer’s disease (AD) represents a promising strategy to identify novel treatments for dementia in AD. Previous findings from our group revealed that the study of aged-Tg2576 cognitive resilient individuals is a suitable tool for this purpose. In the present study, we performed a transcriptomic analysis using the prefrontal cortex of demented and resilient Tg2576 transgenic AD mice. We have been able to hypothesize that pathways involved in inflammation, amyloid degradation, memory function, and neurotransmission may be playing a role on cognitive resilience in AD. Intriguingly, the results obtained in this study are suggestive of a reduction of the influx of peripheral immune cells into the brain on cognitive resilient subjects. Indeed, Cd4 mRNA expression is significantly reduced on Tg2576 mice with cognitive resilience. For further validation of this result, we analyzed CD4 expression in human AD samples, including temporal cortex and peripheral blood mononuclear cells (PBMC). Interestingly, we have found a negative correlation between CD4 mRNA levels in the periphery and the score in the Mini-Mental State Exam of AD patients. These findings highlight the importance of understanding the role of the immune system on the development of neurodegenerative diseases and points out to the infiltration of CD4+ cells in the brain as a key player of cognitive dysfunction in AD.

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Anti-inflammatory Activity of a Polypeptide Fraction From Achyranthes bidentate in Amyloid β Oligomers Induced Model of Alzheimer’s Disease

Frontiers in Pharmacology ◽

10.3389/fphar.2021.716177 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xiangyu Ge ◽

Yitong Wang ◽

Shu Yu ◽

Xuemin Cao ◽

Yicong Chen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Inflammatory Cytokines ◽

Mrna Levels ◽

Bv2 Microglia ◽

M1 Phenotype ◽

Anti Inflammatory ◽

The Brain ◽

M2 Phenotype ◽

Pro Inflammatory Cytokines

Neuroinflammation plays a crucial role in neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), and anti-inflammation has been considered as a potential therapeutic strategy. Achyranthes bidentate polypeptide fraction k (ABPPk) was shown to protect neurons from death and suppress microglia and astrocyte activation in PD model mice. However, how ABPPk regulates neuroinflammation to exert a neuroprotective role remains unclear. Toxic Aβ oligomers (AβOs) can trigger inflammatory response and play an important role in the pathogenesis of AD. In the present study, for the first time, we investigated the effects and underlying mechanisms of ABPPk on neuroinflammation in AβOs-induced models of AD. In vitro, ABPPk pretreatment dose-dependently inhibited AβOs-induced pro-inflammatory cytokines mRNA levels in BV2 and primary microglia. ABPPk pretreatment also reduced the neurotoxicity of BV2 microglia-conditioned media on primary hippocampal neurons. Furthermore, ABPPk down-regulated the AβOs-induced phosphorylation of IκBα and NF-κB p65 as well as the expression of NLRP3 in BV2 microglia. In vivo, ABPPk pre-administration significantly improved locomotor activity, alleviated memory deficits, and rescued neuronal degeneration and loss in the hippocampus of AβOs-injected mice. ABPPk inhibited the activation of microglia in hippocampal CA3 region and suppressed the activation of NF-κB as well as the expression of NLRP3, cleaved caspase-1, and ASC in the brain after AβOs injection. ABPPk hindered the release of pro-inflammatory cytokines and promoted the release of anti-inflammatory cytokines in the brain. Notably, the polarization experiment on BV2 microglia demonstrated that ABPPk inhibited M1-phenotype polarization and promoted M2-phenotype polarization by activating the LPS- or AβOs-impaired autophagy in microglia. Taken together, our observations indicate that ABPPk can restore the autophagy of microglia damaged by AβOs, thereby promoting M2-phenotype polarization and inhibiting M1-phenotype polarization, thus playing a role in regulating neuroinflammation and alleviating neurotoxicity.

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Longitudinal Changes in Individual BrainAGE in Healthy Aging, Mild Cognitive Impairment, and Alzheimer’s Disease

GeroPsych ◽

10.1024/1662-9647/a000074 ◽

2012 ◽

Vol 25 (4) ◽

pp. 235-245 ◽

Cited By ~ 64

Author(s):

Katja Franke ◽

Christian Gaser

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Healthy Aging ◽

Brain Aging ◽

Elderly Subjects ◽

Additional Increase ◽

Longitudinal Changes ◽

Novel Method ◽

The Brain

We recently proposed a novel method that aggregates the multidimensional aging pattern across the brain to a single value. This method proved to provide stable and reliable estimates of brain aging – even across different scanners. While investigating longitudinal changes in BrainAGE in about 400 elderly subjects, we discovered that patients with Alzheimer’s disease and subjects who had converted to AD within 3 years showed accelerated brain atrophy by +6 years at baseline. An additional increase in BrainAGE accumulated to a score of about +9 years during follow-up. Accelerated brain aging was related to prospective cognitive decline and disease severity. In conclusion, the BrainAGE framework indicates discrepancies in brain aging and could thus serve as an indicator for cognitive functioning in the future.

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The Weak Combined Magnetic Fields Reduce the Brain Î²-Amyloid in an Animal Model of Sporadic Alzheimer's Disease

PIERS Online ◽

10.2529/piers081218104003 ◽

2009 ◽

Vol 5 (4) ◽

pp. 311-315 ◽

Cited By ~ 1

Author(s):

Natalia V. Bobkova ◽

Vadim V. Novikov ◽

Natalia I. Medvinskaya ◽

Irina Yu. Aleksandrova ◽

Eugenii E. Fesenko

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Animal Model ◽

Magnetic Fields ◽

Sporadic Alzheimer’S Disease ◽

Combined Magnetic Fields ◽

The Brain

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SPECIFIC PROPERTIES OF TUBULIN IN THE PREFRONTAL CORTEX IN CONTROL, SCHIZOPHRENIA AND VASCULAR DEMENTIA

"Medical & pharmaceutical journal "Pulse" ◽

10.26787/nydha-2686-6838-2020-22-11-65-71 ◽

2020 ◽

pp. 65-71

Author(s):

Burbaeva G.Sh. ◽

Androsova L.V. ◽

Vorobyeva E.A. ◽

Savushkina O.K.

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Prefrontal Cortex ◽

Vascular Dementia ◽

Binding Activity ◽

Nephelometric Method ◽

Rate Of Polymerization ◽

Mental Diseases ◽

And Control ◽

The Brain

The aim of the study was to evaluate the rate of polymerization of tubulin into microtubules and determine the level of colchicine binding (colchicine-binding activity of tubulin) in the prefrontal cortex in schizophrenia, vascular dementia (VD) and control. Colchicine-binding activity of tubulin was determined by Sherlinе in tubulin-enriched extracts of proteins from the samples. Measurement of light scattering during the polymerization of the tubulin was carried out using the nephelometric method at a wavelength of 450-550 nm. There was a significant decrease in colchicine-binding activity and the rate of tubulin polymerization in the prefrontal cortex in both diseases, and in VD to a greater extent than in schizophrenia. The obtained results suggest that not only in Alzheimer's disease, but also in other mental diseases such as schizophrenia and VD, there is a decrease in the level of tubulin in the prefrontal cortex of the brain, although to a lesser extent than in Alzheimer's disease, and consequently the amount of microtubules.

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Electromagnetic field in Alzheimer’s disease: a literature review of recent preclinical and clinical studies

Current Alzheimer Research ◽

10.2174/1567205017666201130085853 ◽

2020 ◽

Vol 17 ◽

Author(s):

Reem Habib Mohamad Ali Ahmad ◽

Marc Fakhoury ◽

Nada Lawand

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurodegenerative Disorder ◽

In Vivo Studies ◽

Key Factors ◽

Potential Benefits ◽

Preclinical And Clinical Studies ◽

The Brain

: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloidbeta (Aβ) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aβ expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.

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

Current Alzheimer Research ◽

10.2174/1567205013666160603011256 ◽

2017 ◽

Vol 14 (4) ◽

pp. 441-452 ◽

Cited By ~ 4

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.

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Role of Nanomedicines in Delivery of Anti-Acetylcholinesterase Compounds to the Brain in Alzheimer’s Disease

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527313666141023100618 ◽

2014 ◽

Vol 13 (8) ◽

pp. 1315-1324 ◽

Cited By ~ 13

Author(s):

Mohammad Ahmad ◽

Javed Ahmad ◽

Saima Amin ◽

Mahfoozur Rahman ◽

Mohammad Anwar ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

The Brain

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Current Strategies and Novel Drug Approaches for Alzheimer Disease

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527319666200717091513 ◽

2020 ◽

Vol 19 (9) ◽

pp. 676-690 ◽

Cited By ~ 2

Author(s):

Roma Ghai ◽

Kandasamy Nagarajan ◽

Meenakshi Arora ◽

Parul Grover ◽

Nazakat Ali ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cholinergic Neurons ◽

Amyloid Plaque ◽

Neural Pathways ◽

Current Trends ◽

Personality Changes ◽

Traditional Therapies ◽

Novel Drug ◽

The Brain

Alzheimer’s Disease (AD) is a chronic, devastating dysfunction of neurons in the brain leading to dementia. It mainly arises due to neuronal injury in the cerebral cortex and hippocampus area of the brain and is clinically manifested as a progressive mental failure, disordered cognitive functions, personality changes, reduced verbal fluency and impairment of speech. The pathology behind AD is the formation of intraneuronal fibrillary tangles, deposition of amyloid plaque and decline in choline acetyltransferase and loss of cholinergic neurons. Tragically, the disease cannot be cured, but its progression can be halted. Various cholinesterase inhibitors available in the market like Tacrine, Donepezil, Galantamine, Rivastigmine, etc. are being used to manage the symptoms of Alzheimer’s disease. The paper’s objective is to throw light not only on the cellular/genetic basis of the disease, but also on the current trends and various strategies of treatment including the use of phytopharmaceuticals and nutraceuticals. Enormous literature survey was conducted and published articles of PubMed, Scifinder, Google Scholar, Clinical Trials.org and Alzheimer Association reports were studied intensively to consolidate the information on the strategies available to combat Alzheimer’s disease. Currently, several strategies are being investigated for the treatment of Alzheimer’s disease. Immunotherapies targeting amyloid-beta plaques, tau protein and neural pathways are undergoing clinical trials. Moreover, antisense oligonucleotide methodologies are being approached as therapies for its management. Phytopharmaceuticals and nutraceuticals are also gaining attention in overcoming the symptoms related to AD. The present review article concludes that novel and traditional therapies simultaneously promise future hope for AD treatment.

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Gut Microbiota and Dysbiosis in Alzheimer’s Disease: Implications for Pathogenesis and Treatment

Molecular Neurobiology ◽

10.1007/s12035-020-02073-3 ◽

2020 ◽

Vol 57 (12) ◽

pp. 5026-5043 ◽

Cited By ~ 2

Author(s):

Shan Liu ◽

Jiguo Gao ◽

Mingqin Zhu ◽

Kangding Liu ◽

Hong-Liang Zhang

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Gut Microbiota ◽

Gut Dysbiosis ◽

Bidirectional Communication ◽

Significant Research ◽

Novel Therapeutic Strategies ◽

The Brain ◽

Brain Homeostasis ◽

Gut Microbiota Composition

Abstract Understanding how gut flora influences gut-brain communications has been the subject of significant research over the past decade. The broadening of the term “microbiota-gut-brain axis” from “gut-brain axis” underscores a bidirectional communication system between the gut and the brain. The microbiota-gut-brain axis involves metabolic, endocrine, neural, and immune pathways which are crucial for the maintenance of brain homeostasis. Alterations in the composition of gut microbiota are associated with multiple neuropsychiatric disorders. Although a causal relationship between gut dysbiosis and neural dysfunction remains elusive, emerging evidence indicates that gut dysbiosis may promote amyloid-beta aggregation, neuroinflammation, oxidative stress, and insulin resistance in the pathogenesis of Alzheimer’s disease (AD). Illustration of the mechanisms underlying the regulation by gut microbiota may pave the way for developing novel therapeutic strategies for AD. In this narrative review, we provide an overview of gut microbiota and their dysregulation in the pathogenesis of AD. Novel insights into the modification of gut microbiota composition as a preventive or therapeutic approach for AD are highlighted.

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