The Toxicity and Polymorphism of β-Amyloid Oligomers

It is widely accepted that β-amyloid oligomers (Aβos) play a key role in the progression of Alzheimer’s disease (AD) by inducing neuron damage and cognitive impairment, but Aβos are highly heterogeneous in their size, structure and cytotoxicity, making the corresponding studies tough to carry out. Nevertheless, a number of studies have recently made remarkable progress in the describing the characteristics and pathogenicity of Aβos. We here review the mechanisms by which Aβos exert their neuropathogenesis for AD progression, including receptor binding, cell membrane destruction, mitochondrial damage, Ca2+ homeostasis dysregulation and tau pathological induction. We also summarize the characteristics and pathogenicity such as the size, morphology and cytotoxicity of dimers, trimers, Aβ*56 and spherical oligomers, and suggest that Aβos may play a different role at different phases of AD pathogenesis, resulting in differential consequences on neuronal synaptotoxicity and survival. It is warranted to investigate the temporal sequence of Aβos in AD human brain and examine the relationship between different Aβos and cognitive impairment.

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P1-266: Uncovering The Relationship Between β-Amyloid and Glucose Metabolism in Mild Cognitive Impairment

Alzheimer s & Dementia ◽

10.1016/j.jalz.2016.06.1016 ◽

2016 ◽

Vol 12 ◽

pp. P516-P517

Author(s):

Felix Carbonell ◽

Donald G. McLaren ◽

Alex P. Zijdenbos ◽

Barry J. Bedell

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Glucose Metabolism ◽

Β Amyloid ◽

The Relationship

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IC-P-105: Uncovering The Relationship Between β-Amyloid and Glucose Metabolism in Mild Cognitive Impairment

Alzheimer s & Dementia ◽

10.1016/j.jalz.2016.06.135 ◽

2016 ◽

Vol 12 ◽

pp. P79-P80

Author(s):

Felix Carbonell ◽

Donald G. McLaren ◽

Alex P. Zijdenbos ◽

Barry J. Bedell

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Glucose Metabolism ◽

Β Amyloid ◽

The Relationship

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Neurochemical Aspects of Alzheimer’s Disease and Movement Disturbances: A Theory of β-Amyloid and τ-Protein

American Journal of Alzheimer s Disease & Other Dementias® ◽

10.1177/1533317518790631 ◽

2018 ◽

Vol 33 (8) ◽

pp. 535-540 ◽

Cited By ~ 2

Author(s):

Auda Fares ◽

Dieter Borrmann

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Cognitive Deficits ◽

Large Body ◽

Motor Dysfunction ◽

Amyloid Aβ ◽

Β Amyloid ◽

Τ Protein ◽

The Relationship

The pathologic and molecular substrate of people diagnosed with cognitive deficits and movement disturbance may not occur exclusively in the context of a brain region, but it may be expressed in another part of body such as muscle. A large body of research has demonstrated that slow motor performance is associated with cognitive impairment in elderly people. The interdependence between motor dysfunction and cognition decline is still not fully understood. Although several factors have been suggested to give a plausible explanation, β-amyloid (Aβ) and τ-protein aggregation is a common feature of a number of neurodegenerative disorders which are characterized by both motor and cognitive impairment, and it is assumed that the aggregation process plays a central role in the pathogenesis of cognitive impairment and motor dysfunction in Alzheimer’s disease. The purpose of the present review is to provide an overview of the available evidence that can help to better elucidate the pathophysiological mechanisms underlying the relationship between cognitive and movement disturbances by focusing on Aβ and τ-protein.

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The Relationship Between Level of Cognitive Impairment and Treatment in Patients with Paranoid Schizophrenia

10.26226/morressier.5a6ef3f0d462b80290b58bc5 ◽

2018 ◽

Author(s):

Nataliia Petrova

Keyword(s):

Cognitive Impairment ◽

Paranoid Schizophrenia ◽

The Relationship

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NEUROPSYCHOLOGICAL CHANGES IN PATIENTS WITH A CONSEQUENCE OF TRAUMATIC BRAIN INJURY

JOURNAL OF NEUROLOGY AND NEUROSURGICAL RESEARCH ◽

10.26739/2181-0982-2020-3-9 ◽

2020 ◽

Vol 3 (1) ◽

pp. 44-46

Author(s):

Istatillo Shodjalilov ◽

◽

Saoda Igamova ◽

Aziza Djurabekova

Keyword(s):

Traumatic Brain Injury ◽

Cognitive Impairment ◽

Brain Injury ◽

Neuropsychological Testing ◽

Anxiety And Depression ◽

Psychopathological Symptoms ◽

Neuropsychological Changes ◽

The Relationship

The incidence of cognitive impairment in TBI is high, depending on the severity. At the same time, psychopathological symptoms in the form of asthenia, increased anxiety and depression are encountered among patients with TBI. The work studied the relationship between cognitive and psychopathological symptoms in patients with TBI using neuropsychological testing on scales.

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Evaluación Cognitiva Montreal y consumo de alcohol: Un diagnóstico descriptivo del deterioro cognitivo en estudiantes universitarios de Durango, México

Revista de Técnicas de Enfermería y Salud ◽

10.35429/jnt.2019.7.3.28.38 ◽

2019 ◽

pp. 28-38

Author(s):

Karla Liliana Pérez-Sosa ◽

Edgar Felipe Lares-Bayona

Keyword(s):

Cognitive Impairment ◽

Alcohol Consumption ◽

Cognitive Functions ◽

Toxic Substance ◽

Female Gender ◽

Diagnostic Tools ◽

Cross Sectional ◽

Probabilistic Study ◽

The Central Nervous System ◽

The Relationship

Alcohol is a toxic substance associated with acute and chronic disorders affecting the Central Nervous System and significantly altering brain function. Objective: To determine the relationship between cognitive impairment and alcohol consumption in university students of the Juárez University of the State of Durango. Methodology: It is a cross-sectional, descriptive, comparative, non-probabilistic study, for convenience. A database was designed on the results obtained in a clinical interview on alcohol consumption and the application of the Montreal Cognitive Assessment (MoCA) test. Contribution: The evaluation of cognitive functions show similar results, the male sex presented a better score in Attention and the female one in Orientation. More involvement was identified in the Deferred Memory functions in both groups. In relation to alcohol consumption, the cognitive functions evaluated show lower levels. The female gender was more evident cognitive impairment in relation to alcohol consumption being statistically significant (p <0.025). Alcohol consumption is a risky behavior that deserves to be recognized by the main actors about neurocognitive effects. Alcohol consumption prevention programs and cognitive diagnostic tools are appropriate strategies to reduce risk behaviors in mental health.

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Alzheimer’s Disease: Erythrocyte 2,3-diphosphoglycerate Content and Circulating Erythropoietin

Current Alzheimer Research ◽

10.2174/1567205016666190827120108 ◽

2019 ◽

Vol 16 (9) ◽

pp. 834-835

Author(s):

Petter Järemo ◽

Alenka Jejcic ◽

Vesna Jelic ◽

Tasmin Shahnaz ◽

Homira Behbahani ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Cell Damage ◽

Control Group ◽

Red Cell ◽

Oxygen Release ◽

Regulatory Pathways ◽

Β Amyloid ◽

2,3 Dpg

Background: Alzheimer’s Disease (AD) features the accumulation of β-amyloid in erythrocytes. The subsequent red cell damage may well affect their oxygen-carrying capabilities. 2,3- diphosphoglycerate (2,3-DPG) binds to the hemoglobin thereby promoting oxygen release. It is theorized that 2,3-DPG is reduced in AD and that the resulting hypoxia triggers erythropoietin (EPO) release. Methods & Objective: To explore this theory, we analyzed red cell 2,3-DPG content and EPO in AD, mild cognitive impairment, and the control group, subjective cognitive impairment. Results: We studied (i) 2,3-DPG in red cells, and (ii) circulating EPO in AD, and both markers were unaffected by dementia. Disturbances of these oxygen-regulatory pathways do not appear to participate in brain hypoxia in AD.

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MiR-335-5p Inhibits β-Amyloid (Aβ) Accumulation to Attenuate Cognitive Deficits Through Targeting c-jun-N-terminal Kinase 3 in Alzheimer’s Disease

Current Neurovascular Research ◽

10.2174/1567202617666200128141938 ◽

2020 ◽

Vol 17 (1) ◽

pp. 93-101 ◽

Cited By ~ 3

Author(s):

Dan Wang ◽

Zhifu Fei ◽

Song Luo ◽

Hai Wang

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Transgenic Mice ◽

Western Blot ◽

Mrna Expression ◽

Cognitive Deficits ◽

Protein Levels ◽

Amyloid Aβ ◽

Β Amyloid ◽

The Relationship

Objectives: Alzheimer's disease (AD), also known as senile dementia, is a common neurodegenerative disease characterized by progressive cognitive impairment and personality changes. Numerous evidences have suggested that microRNAs (miRNAs) are involved in the pathogenesis and development of AD. However, the exact role of miR-335-5p in the progression of AD is still not clearly clarified. Methods: The protein and mRNA levels were measured by western blot and RNA extraction and quantitative real-time PCR (qRT-PCR), respectively. The relationship between miR-335-5p and c-jun-N-terminal kinase 3 (JNK3) was confirmed by dual-luciferase reporter assay. SH-SY5Y cells were transfected with APP mutant gene to establish the in vitro AD cell model. Flow cytometry and western blot were performed to evaluate cell apoptosis. The APP/PS1 transgenic mice were used as an in vivo AD model. Morris water maze test was performed to assess the effect of miR- 335-5p on the cognitive deficits in APP/PS1 transgenic mice. Results: The JNK3 mRNA expression and protein levels of JNK3 and β-Amyloid (Aβ) were significantly up-regulated, and the mRNA expression of miR-335-5p was down-regulated in the brain tissues of AD patients. The expression levels of miR-335-5p and JNK3 were significantly inversely correlated. Further, the dual Luciferase assay verified the relationship between miR-335- 5p and JNK3. Overexpression of miR-335-5p significantly decreased the protein levels of JNK3 and Aβ and inhibited apoptosis in SH-SY5Y/APPswe cells, whereas the inhibition of miR-335-5p obtained the opposite results. Moreover, the overexpression of miR-335-5p remarkably improved the cognitive abilities of APP/PS1 mice. Conclusion: The results revealed that the increased JNK3 expression, negatively regulated by miR-335-5p, may be a potential mechanism that contributes to Aβ accumulation and AD progression, indicating a novel approach for AD treatment.

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A Biomarker Combining Imaging and Neuropsychological Assessment for Tracking Early Alzheimer's Disease in Clinical Trials

Current Alzheimer Research ◽

10.2174/1567205014666171106150309 ◽

2018 ◽

Vol 15 (5) ◽

pp. 429-442 ◽

Cited By ~ 3

Author(s):

Nishant Verma ◽

S. Natasha Beretvas ◽

Belen Pascual ◽

Joseph C. Masdeu ◽

Mia K. Markey ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Trials ◽

Cognitive Impairment ◽

Latent Variable ◽

Brain Regions ◽

Disease Assessment ◽

Latent Variable Analysis ◽

The Relationship ◽

Selection Of

Background: Combining optimized cognitive (Alzheimer's Disease Assessment Scale- Cognitive subscale, ADAS-Cog) and atrophy markers of Alzheimer's disease for tracking progression in clinical trials may provide greater sensitivity than currently used methods, which have yielded negative results in multiple recent trials. Furthermore, it is critical to clarify the relationship among the subcomponents yielded by cognitive and imaging testing, to address the symptomatic and anatomical variability of Alzheimer's disease. Method: Using latent variable analysis, we thoroughly investigated the relationship between cognitive impairment, as assessed on the ADAS-Cog, and cerebral atrophy. A biomarker was developed for Alzheimer's clinical trials that combines cognitive and atrophy markers. Results: Atrophy within specific brain regions was found to be closely related with impairment in cognitive domains of memory, language, and praxis. The proposed biomarker showed significantly better sensitivity in tracking progression of cognitive impairment than the ADAS-Cog in simulated trials and a real world problem. The biomarker also improved the selection of MCI patients (78.8±4.9% specificity at 80% sensitivity) that will evolve to Alzheimer's disease for clinical trials. Conclusion: The proposed biomarker provides a boost to the efficacy of clinical trials focused in the mild cognitive impairment (MCI) stage by significantly improving the sensitivity to detect treatment effects and improving the selection of MCI patients that will evolve to Alzheimer’s disease.

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