scholarly journals Disrupted core-periphery structure of multimodal brain networks in Alzheimer’s disease

2019 ◽  
Vol 3 (2) ◽  
pp. 635-652 ◽  
Author(s):  
Jeremy Guillon ◽  
Mario Chavez ◽  
Federico Battiston ◽  
Yohan Attal ◽  
Valentina La Corte ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Impairment ◽  
Large Scale ◽  
Brain Connectivity ◽  
Functional Integration ◽  
The Core ◽  
Multiplex Network ◽  
Different Types

In Alzheimer’s disease (AD), the progressive atrophy leads to aberrant network reconfigurations both at structural and functional levels. In such network reorganization, the core and peripheral nodes appear to be crucial for the prediction of clinical outcome because of their ability to influence large-scale functional integration. However, the role of the different types of brain connectivity in such prediction still remains unclear. Using a multiplex network approach we integrated information from DWI, fMRI, and MEG brain connectivity to extract an enriched description of the core-periphery structure in a group of AD patients and age-matched controls. Globally, the regional coreness—that is, the probability of a region to be in the multiplex core—significantly decreased in AD patients as result of a random disconnection process initiated by the neurodegeneration. Locally, the most impacted areas were in the core of the network—including temporal, parietal, and occipital areas—while we reported compensatory increments for the peripheral regions in the sensorimotor system. Furthermore, these network changes significantly predicted the cognitive and memory impairment of patients. Taken together these results indicate that a more accurate description of neurodegenerative diseases can be obtained from the multimodal integration of neuroimaging-derived network data.

Biophysical insights into the membrane interaction of the core amyloid-forming Aβ40fragment K16–K28 and its role in the pathogenesis of Alzheimer's disease

2016 ◽  
Vol 18 (25) ◽  
pp. 16890-16901 ◽  
Author(s):  
Swapna Bera ◽  
Kyle J. Korshavn ◽  
Rajiv K. Kar ◽  
Mi Hee Lim ◽  
Ayyalusamy Ramamoorthy ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hydrophobic Region ◽  
Membrane Interaction ◽  
The Core

Role of central hydrophobic region of Aβ40 in membrane interaction.

scholarly journals Role of Endoplasmic Reticulum Stress in Learning and Memory Impairment and Alzheimer's Disease-Like Neuropathology in the PS19 and APPSwe Mouse Models of Tauopathy and Amyloidosis

eNeuro ◽  
2017 ◽  
Vol 4 (4) ◽  
pp. ENEURO.0025-17.2017 ◽  
Author(s):  
Denise Isabelle Briggs ◽  
Erwin Defensor ◽  
Pooneh Memar Ardestani ◽  
Bitna Yi ◽  
Michelle Halpain ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Learning And Memory ◽  
Mouse Models ◽  
Memory Impairment

Novel Therapeutic Mechanism of Action of Metformin and Its Nanoformulation in Alzheimer's Disease and Role of AKT/ERK/GSK Pathway.

2021 ◽  
Author(s):  
Harish Kumar ◽  
Amitava Chakrabarti ◽  
Phulen Sarma ◽  
Manish Modi ◽  
Dibyajyoti Banerjee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Control ◽  
Rat Model ◽  
Memory Impairment ◽  
Protective Efficacy ◽  
Control Group ◽  
Hyperphosphorylated Tau ◽  
Days Of Therapy

Abstract Background: Insulin resistance in brain plays a critical role in the pathogenesis of Alzheimer's disease (AD). Metformin is a blood brain barrier crossing anti-diabetic insulin-sensitizer drug. Current study has evaluated the therapeutic and mechanistic role of conventional as well as solid lipid nanoformulation (SLN) of metformin in intracerebro ventricular (ICV) Aβ (1-42) rat-model of AD. Methods: SLN-metformin was prepared by the micro-emulsification method and further evaluated by zetasizer and scanning electron-microscopy. In the animal experimental phase, AD was induced by bilateral ICV injection of Aβ using stereotaxic technique, whereas control group (sham) received ICV-NS. 14 days post-model induction, ICV- Aβ treated rats were further divided into 5 groups: disease control (no treatment), Metformin dose of (50mg/kg, 100mg/kg and 150 mg/kg), SLN of metformin 50mg/kg and memantine 1.8mg/kg (positive-control). Animals were tested for cognitive performance (in EPM, MWM) after 21 days of therapy, and then sacrificed. Brain homogenate was evaluated using ELISA for (Aβ (1-42), hyperphosphorylated tau, pAKTser473, GSK-3β, p-ERK,) and HPLC (metformin level). Brain histopathology was used to evaluate neuronal injury score (H&E) and Bcl2 and BAX (IHC). Results: The average size of SLN-metformin was <200 nm and was of spherical in shape with 94.08% entrapment efficiency. Compared to sham, the disease-control group showed significantly higher (p≤0.05) memory impairment (in MWM and EPM), higher hyperphosphorylated tau, Aβ (1-42), and Bax and lower Bcl-2 expression. Metformin was detectable in brain. Treatment with metformin and its SLN form significantly decreased the memory impairment as well as decreased the expression of hyperphosphorylated tau, Aβ(1-42), Bax expression and increased expression of Bcl-2 in brain. AKT-ERK-GSK3β-Hyperphosphorylated tau pathway can be implicated in the protective efficacy of metformin. Conclusion: Both metformin and SLN metformin is found to be effective as therapeutic agent in ICV-AB rat model of AD. AKT-ERK-GSK3β-Hyperphosphorylated tau pathway is found to be involved in the protective efficacy of metformin.

Animal models of Alzheimer’s Disease

2017 ◽  
Author(s):  
David Morgan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Drug Development ◽  
Memory Impairment ◽  
Disease Symptoms ◽  
Disease Condition ◽  
Different Types ◽  
Models Of Disease ◽  
Proof Of Principle

In the discovery phase of drug development for Alzheimer’s disease it is useful to have animal models in which proof of principle can be obtained. Models of disease symptoms (memory impairment) and models of the disease pathology (lesions, amyloid-depositing models, tau-depositing models) are described and discussed. Moreover, these different types of models can be combined in an attempt to more faithfully replicate the disease condition. Although worms, flies, fish and dogs have been explored, the bulk of the research has focused on rodents, especially mice. Each of these approaches has limitations, but all have contributed to the development of agents designed to prevent or treat Alzheimer’s and other dementias.

Current Pathogenesis of Alzheimer’s Disease and Plants Derived Neuroprotective Phytoconstituents: A Comprehensive Review

2021 ◽  
Vol 10 ◽  
Author(s):  
Anil Kumar Pradhan ◽  
Bimala Tripathy ◽  
Bimalendu Chowdhury ◽  
Sasmita Kumari Acharjya ◽  
Rajaram Das
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Neurodegenerative Disorders ◽  
Neuroprotective Effect ◽  
Vital Role ◽  
Bioactive Constituents ◽  
Different Types

Background: The exact pathogenesis of Alzheimer’s disease is still a matter to debate, currently there is no reliable therapy established for Alzheimer’s disease. However, several pieces of evidence suggest that the use of plant based phytoconstituents mainly delays the onset of Alzheimer. So, in this review, we collect information about the cause of Alzheimer’s disease hypothesis and neuroprotective effect of phytoconstituents. Objective: This review paper aimed to analyze the current pathogenesis of Alzheimer’s disease and the therapeutic effect of plant phytoconstituents that play a vital role in neuroprotective and antistress activities in Alzheimer’s disease and other neurodegenerative disorders. Methods: The source of literature review obtained from Scopus, Science direct, PubMed, web of science database, and journal by using Alzheimer’s pathogenesis, neuroinflammation, oxidative stress, amyloid beta, flavonoids, alkaloids are important part of these review research. Results: The current review explored the different types of pathogenesis involved in Alzheimer’s disease and the role of phytoconstituents in treatment of it. The collected information showed that plant based constituents inhibit the major cause of Alzheimer’s disease related to amyloid beta, tau protein, oxidative stress, neuroinflammation etc. Conclusion: The study provide the clue for the investigation of eminent bioactive constituents may serves as an alternative candidate against Alzheimer’s disease and other neurodegenerative disorders.

scholarly journals Age-dependent Shift in the de Novo Proteome Accompanies Pathogenesis in an Alzheimer’s Disease Mouse Model

2020 ◽  
Author(s):  
Megan Elder ◽  
Hediye Erdjument-Bromage ◽  
Mauricio Oliveira ◽  
Maggie Mamcarz ◽  
Thomas Neubert ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Synthesis ◽  
Memory Impairment ◽  
Large Scale ◽  
De Novo ◽  
Neurodegenerative Disorder ◽  
Molecular Abnormalities ◽  
Age Related ◽  
Large Clusters

Abstract Alzheimer’s disease (AD) is an age-related neurodegenerative disorder, however neuropathological changes begin years before memory impairment. Investigation of the early molecular abnormalities in AD might offer innovative opportunities to target memory impairment prior to onset. Decreased protein synthesis plays a fundamental role in AD, yet the consequences of this dysregulation for cellular function remain unknown. We hypothesize that alterations in the de novo proteome drive early metabolic alterations in the hippocampus that persist throughout AD progression. Using a combinatorial amino acid tagging approach to selectively label and enrich newly synthesized proteins, we found that the de novo proteome is disturbed in young APP/PS1 mice prior to symptom onset, affecting the synthesis of multiple components of the synaptic, lysosomal and mitochondrial pathways. Furthermore, the synthesis of large clusters of ribosomal subunits were affected throughout development. Our data suggest that large-scale changes in protein synthesis could underlie cellular dysfunction in AD.

Frontal Defects Contribute to the Genesis of Closing-in in Alzheimer's Disease Patients

2013 ◽  
Vol 19 (7) ◽  
pp. 802-808 ◽  
Author(s):  
Natascia De Lucia ◽  
Dario Grossi ◽  
Angiola Maria Fasanaro ◽  
Sabrina Carpi ◽  
Luigi Trojano
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Prospective Study ◽  
Inhibitory Control ◽  
Neuropsychological Assessment ◽  
Original Model ◽  
Different Types ◽  
Severe Impairment ◽  
Neuropsychological Tasks

AbstractClosing-in (CI) refers to copying drawings near to or superimposed on the original model, and is often observed in Alzheimer's disease (AD) patients. Contrasting hypotheses have been suggested to explain CI, but no prospective study has directly verified these interpretations. We evaluated the role of frontal/executive versus visuo-spatial impairments in a prospective sample of AD patients, and also explored whether different types of CI are related to specific neuropsychological tasks. We enrolled 64 AD patients who underwent copying tasks and an extensive neuropsychological assessment of visuo-spatial and visuo-constructional skills, frontal/executive abilities and anterograde memory. AD patients with CI showed more severe impairment on frontal/executive functions than AD patients without CI. Moreover, the tendency to produce copies superimposed on the model was selectively associated with poor inhibitory control for irrelevant responses. On this basis, we suggest that different CI phenomena could be ascribed to distinctive frontal/executive defects. (JINS, 2013, 19, 1–7)

scholarly journals Hepatocyte Growth Factor in Synaptic Plasticity and Alzheimer's Disease

2010 ◽  
Vol 10 ◽  
pp. 457-461 ◽  
Author(s):  
Shiv K. Sharma
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Receptor Tyrosine Kinase ◽  
Hippocampal Neurons ◽  
Different Types ◽  
Hepatocyte Growth

The hepatocyte growth factor (HGF) was initially identified as a protein that promoted growth of hepatocytes. It regulates proliferation and survival of different types of cells. HGF signaling, which is initiated by its binding to a receptor tyrosine kinase, plays critical roles during development. HGF and its receptor are also present in brain cells. This review describes the role of HGF in hippocampal neurons, synaptic plasticity, and the memory impairment condition, Alzheimer's disease.

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