Amyloid Beta Clearance In Alzheimer S Disease

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Amyloid Beta Clearance In Alzheimer S Disease

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Author : Robert Marr
language : en
Publisher: Frontiers Media SA
Release Date : 2015-03-24

Amyloid Beta Clearance In Alzheimer S Disease written by Robert Marr and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-03-24 with Neurosciences. Biological psychiatry. Neuropsychiatry categories.

Strong evidence continues to accumulate indicating that amyloid-beta (Aß) is a central part of Alzheimer’s disease (AD) pathogenesis in spite of the negative evidence coming from failed clinical trials. Therefore, mechanisms of clearance of Aß are of great interest in understanding AD pathogenesis and the development of effective treatments. This topic focuses on the issues related to Aß clearance in AD. The topics covered include proteases that degrade Aß and their localization, regulation, and functions. This topic also covers issues related to clearance through uptake by glia and through low-density lipoprotein (LDL) receptor mediated mechanisms. Signal transduction related to AD pathology and clearance is also addressed. Finally, immunotherapy and other novel therapeutic approaches are discussed.

Clearance Of Amyloid Beta In Alzheimer S Disease

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Author : Yan-Jiang Wang
language : en
Publisher:
Release Date : 2006

Clearance Of Amyloid Beta In Alzheimer S Disease written by Yan-Jiang Wang and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2006 with Alzheimer's disease categories.

Clearance Of Amyloid Beta Protein In Alzheimer S Disease

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Author : Alicia Mary Hoag
language : en
Publisher:
Release Date : 2001

Clearance Of Amyloid Beta Protein In Alzheimer S Disease written by Alicia Mary Hoag and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2001 with categories.

Effects Of Anti A Beta Monoclonal Antibodies On The Amyloid Beta Peptide Fibrillogenesis And Their Involvement In The Clearance Of Alzheimer S Disease Plaques

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Author : Jeffy Pilar Jiménez
language : en
Publisher:
Release Date : 2010

Effects Of Anti A Beta Monoclonal Antibodies On The Amyloid Beta Peptide Fibrillogenesis And Their Involvement In The Clearance Of Alzheimer S Disease Plaques written by Jeffy Pilar Jiménez and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with categories.

ABSTRACT: Alzheimer's disease (AD) is the most common cause of senile dementia worldwide. AD is a neurodegenerative disorder characterized by the loss of memory and language skill, collapse of the cognitive function, and distortion of social behavior. As of today, the onset mechanisms of AD and cure are unknown; however, three hallmarks are commonly encountered: extra and intracellular accumulation of amyloid beta (ABeta) peptide plaques, formation of intracellular neurofibrillary tangles, and inevitable neuronal death. Hypothetically, a possible scenario provoking or involved in the onset of AD is a cascade effect that starts with an imbalance in the production and clearance of ABeta peptide that consequently leads to its accumulation, formation of tau protein tangles and neuronal death. This work studied and characterized the mechanisms governing ABeta peptide aggregation and the effects of using anti-ABeta monoclonal antibodies to modify this process. These mechanisms play an important role in the formation of AD plaques and are critical in the search for therapies involving ABeta peptide plaque clearance. Yet, antibody-based therapies for plaque clearance are not well understood, adding to the existing concerns about side effects in humans, hence there is a necessity of knowledge in this matter. In this work different N-terminus, C-terminus, and Mid-domain antibodies were used against ABeta peptide species (monomers, oligomers, and fibrils) to probe peptide aggregates modification and disruption. Additionally, construction of a soft supported lipid bilayer membrane was proposed to study the adhesion mechanisms of ABeta peptide and interactions with antibodies, mimicking the neuronal cell surface. The main characterization techniques used in this work were: atomic force microscopy (AFM) and transmission electron microscopy that allowed the physical exploration and visualization of the different processes of aggregation in terms of adhesion, size evolution, and distribution of the peptide; and attenuated total reflectance Fourier spectroscopy (ATR/FTIR) which allowed monitoring the change of secondary structures for the peptide during the processes studied. It is endeavored that this work will help to elucidate the effects attributed to the molecular interactions between ABeta peptide species and antibodies to target ABeta plaque's clearance in the brain of AD patients. Ultimately, this study provides novel information critical for the formulation of effective therapies to prevent and treat AD with less collateral effects. It also represents a contribution to the basic scientific knowledge regarding peptide-antibody interactions with application to other diseases related to protein misfolding.

Beta Amyloid Peptides Extracellular And Intracellular Mechanisms Of Clearance In Alzheimer S Disease

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Author : Luis F. Hernández-Zimbrón
language : en
Publisher:
Release Date : 2016

Beta Amyloid Peptides Extracellular And Intracellular Mechanisms Of Clearance In Alzheimer S Disease written by Luis F. Hernández-Zimbrón and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016 with Medicine categories.

Alzheimer S Disease Cellular And Molecular Aspects Of Amyloid Beta

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Author : J. Robin Harris
language : en
Publisher: Springer Science & Business Media
Release Date : 2006-11-22

Alzheimer S Disease Cellular And Molecular Aspects Of Amyloid Beta written by J. Robin Harris and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2006-11-22 with Science categories.

To understand Alzheimer's disease (AD) is one of the major thrusts of present-day clinical research, strongly supported by more fimdamental cellular, biochemical, immunological and structural studies. It is these latter that receive attention within this book. This compilation of 20 chapters indicates the diversity of work currently in progress and summarizes the current state of knowledge. Experienced authors who are scientifically active in their fields of study have been selected as contributors to this book, in an attempt to present a reasonably complete survey of the field. Inevitably, some exciting topics for one reason or another have not been included, for which we can only apologize. Standardization of terminology is often a problem in science, not least in the Alzheimer field; editorial effort has been made to achieve standardization between the Chapters, but some minor yet acceptable personal / author variation is still present, i. e. P-amyloid/amyloid-P; Ap42/Apl-42/APi. 42! The book commences with a broad survey of the contribution that the range of available microscopical techniques has made to the study of Alzheimer's amyloid plaques and amyloid fibrillogenesis. This chapter also serves as an Introduction to the book, since several of the topics introduced here are expanded upon in later chapters. Also, it is significant to the presence of this chapter that the initial discovery of brain plaques, by Alois Alzheimer, utilized light microscopy, a technique that continues to be extremely valuable in present-day AD research.

Autophagy Induced Beta Amyloid Clearance In Alzheimer S Disease

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Author : Abubakar Wani
language : en
Publisher:
Release Date : 2024-01-23

Autophagy Induced Beta Amyloid Clearance In Alzheimer S Disease written by Abubakar Wani and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2024-01-23 with Health & Fitness categories.

In Autophagy-Induced Beta Amyloid Clearance in Alzheimer's Disease, Abubakar Wani provides a comprehensive overview of the role of autophagy in the clearance of beta-amyloid, a key pathological hallmark of Alzheimer's disease. The book presents the latest research and experimental evidence supporting the use of autophagy as a potential therapeutic target for the treatment of Alzheimer's disease. The book begins with an overview of the cellular mechanisms of autophagy and its role in protein degradation, followed by a discussion of the pathophysiology of Alzheimer's disease and the role of beta-amyloid in disease progression. Wani then explores the molecular mechanisms by which autophagy can promote the clearance of beta-amyloid, including the regulation of autophagy by different signaling pathways and the role of autophagy in mediating the turnover of different protein aggregates. The author also discusses the potential use of autophagy-inducing drugs as a therapeutic strategy for Alzheimer's disease, highlighting the current progress and challenges in the development of autophagy-targeting drugs. Additionally, the book covers the latest research on the role of autophagy in the clearance of other protein aggregates implicated in neurodegenerative diseases. Overall, Autophagy-Induced Beta Amyloid Clearance in Alzheimer's Disease is a valuable resource for researchers, clinicians, and students interested in the molecular mechanisms underlying Alzheimer's disease and the potential therapeutic applications of autophagy induction. The book provides a comprehensive and up-to-date review of the latest research in the field, making it an essential reference for anyone working in this area.

The Role Of Annexin A1 In The Regulation Of Amyloid Beta Clearance Neuroinflammation And Blood Brain Barrier Functionality In Alzheimer S Disease

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Author : Miriam Ries
language : en
Publisher:
Release Date : 2017

The Role Of Annexin A1 In The Regulation Of Amyloid Beta Clearance Neuroinflammation And Blood Brain Barrier Functionality In Alzheimer S Disease written by Miriam Ries and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017 with categories.

Magnetic Nanoparticle Hyperthermia Mediated Clearance Of Beta Amyloid Plaques

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Author : Eric D. Dyne
language : en
Publisher:
Release Date : 2021

Magnetic Nanoparticle Hyperthermia Mediated Clearance Of Beta Amyloid Plaques written by Eric D. Dyne and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021 with categories.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by the accumulation of beta-amyloid plaques and neurofibrillary hyperphosphorylated tau tangles. According to the most recent report from the U.S. Centers for Disease Control and Prevention, Alzheimer's disease is the 6th leading cause of death in the United States and the number of cases as increased almost 150% in the last 20 years in the United States. The disease starts as a subtle change in memory that progresses into noticeable cognitive decline, often referred to as mild cognitive impairment, and progresses into severe and pervasive memory loss. One of the hallmarks of Alzheimer's disease is the accumulation of the misfolded protein product of the amyloid precursor protein, beta-amyloid. Beta-amyloid has been long considered and widely supported by genetics and biochemical observation to promote Alzheimer's disease pathology. One of the earliest and long-supported theories, the amyloid hypothesis, posits beta-amyloid accumulation as having a central role in the pathogenesis of Alzheimer's disease as a promoter of tau seeding and inflammatory signaling which causes immune dysfunction. Beta-amyloid therapeutics represent the majority of the clinical trial candidates for Alzheimer's disease therapeutics. Recent clinical failures of anti-beta-amyloid trials, including Aducanumab and Gantenerumab, have raised concerns for the ability to manage beta-amyloid accumulation. The current pipeline of drugs targeting both beta-amyloid and tau are ineffective; therefore warranting alternative therapeutic options. A possible alternative non-pharmacological option for targeting beta-amyloid plaque aggregation is using energy to disrupt large beta-amyloid plaques into smaller fragments that may be cleared by microglia, the innate immune cells of the brain. One manner in which we can generate sufficient energy in a minimal to non-invasive safe manner is to use an alternating magnetic field (AMF). When conductive materials, such as superparamagnetic materials, are exposed to AMF, a controllable amount of thermal energy can be generated. The use of high-frequency alternating magnetic field generation has been used for many biomedical applications such as tumor resection and biofilm targetting. It has been observed that beta-amyloid plaques are held together by both hydrogen bonds and hydrophobic interactions within the beta-amyloid plaque structure. Our approach relies upon the interaction between 20nm superparamagnetic iron (II,III) oxide (Fe3O4) nanoparticles (MNP) and remote application of mild hyperthermia by an external magnetic field. After successful fragmentation, microglia processed the fragmented beta-amyloid for removal. It is hypothesized that the removal of the beta-amyloid plaques will attenuate pro-inflammatory signaling and our results demonstrated attenuation of several pro-inflammatory genes after exposure to mild hyperthermia. The application of mild hyperthermia to microglia induces professional chaperones known as heat shock proteins (HSP)7. These proteins play a vital role in the proper configuration of proteins but also act as antigen presenting cells. It is hypothesized that approximately 30% of newly synthesized proteins are not properly folded or formed Heat shock protein functionally should remove beta-amyloid, however, this does not seem to happen in Alzheimer's disease. The use of mild-hyperthermia promotes a heat-stress response that activates HSP expression. We hypothesize that HSP70, a member of the HSP family involved with phagocytosis and autophagy, may produce a functional role of microglia towards clearing the beta-amyloid fragments. This study will address the specific aims using isolated human microglia from an adult patient (C20) microglia as our in vitro model organism. Beyond the depths of this dissertation, additional work will characterize our approach in an in vivo model of AD to further validate our in vitro observations. The use of human microglia provides our approach the opportunity of continuity with human reagents and understanding the human transcriptomic response to treatment. Further, the cell line chosen is superior to other commercially available cell lines in that the C20 cells readily endocytosed beta-amyloid fragments, released a wide variety of signaling molecules, and were IBA1 positive; all features were seen to be altered in the commercially available HMC3 cell line. Collectively, we propose using mild-hyperthermia to disrupt large beta-amyloid plaques via magnetic nanoparticles to reduce inflammatory signaling and promote clearance, possibly mediated by heat-shock induced HSP70.

Apolipoprotein E And Alzheimer S Disease

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Author : A.D. Roses
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-12-06

Apolipoprotein E And Alzheimer S Disease written by A.D. Roses and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-12-06 with Medical categories.

There is now considerable genetic evidence that the type 4 allele of the apolipoprotein E gene is a major susceptibility factor associated with late-onset Alzheimer's disease, the common form of the disease defined as starting after sixty years of age. The role of apolipoprotein E in normal brain metabolism and in the pathogenesis of Alzheimer's disease are new and exciting avenues of research. This book, written by the most outstanding scientists in this new filed, is the first presentation of results concerning the implications of apolipoprotein E on the genetics, cell biology, neuropathology, biochemistry, and therapeutic management of Alzheimer's disease.