Alzheimer's Disease From Molecular Mechanisms to Clinical Practices


Book Description

“Alzheimer’s Disease: From Molecular Mechanisms to Clinical Practices” explores the extensive perspective from the molecular foundations to the clinical diagnosis and treatment of Alzheimer’s disease. The book serves as a fundamental resource for understanding the neurobiological basis and molecular pathogenesis of Alzheimer’s, while also discussing the challenges and opportunities of transitioning from the laboratory to clinical settings. The initial sections of the book comprehensively examine the fundamental molecular characteristics of Alzheimer’s disease; these include the accumulation of amyloid-beta peptide, hyperphosphorylation of tau protein, and how these processes lead to synaptic dysfunction and neuronal death. These chapters provide strategies on how to understand the pathology of the disease at a molecular level and how this knowledge can be translated into clinical practice. Subsequent parts focus on the development and use of biomarkers for the early diagnosis of Alzheimer’s disease. In addition to the role of genetic predispositions, the effects of environmental factors and lifestyle choices on Alzheimer’s disease are discussed, highlighting the multifactorial nature of the disease. In conclusion, this book is a valuable resource for clinicians, researchers, and medical students specializing in the field. It provides essential scientific and practical information necessary for a better understanding and management of Alzheimer’s disease, offering a comprehensive perspective on the integration of molecular mechanisms with clinical applications.




Alzheimer's Disease


Book Description

Alzheimer's disease is the most common cause of senile dementia. Since the discovery in 1984 of the amyloid ?-peptide (A?) as the core protein of the senile plaques present in the brains of Alzheimer's disease sufferers, an immense amount of research has gone into mapping out the molecular basis of this debilitating disease. The aim of Alzheimer's Disease: Methods and Protocols is to bring together the main biochemical, cell biological, and molecular biological techniques and approaches that are being used to investigate the molecular basis of Alzheimer's disease. This volume begins with chapters of an introductory/ review nature. Chapter 1 provides a historical introduction to Alzheimer's d- ease with particular emphasis on the central role played by A? and its re- tion to tau. Chapter 2 examines the genetics underlying this neurodegenerative disease, covering the amyloid precursor protein, apolipoprotein E, and the presenilins. Chapter 3 presents an overview of currently available therapeutic agents and prospects for drugs of the future.




Neurodegenerative Diseases


Book Description

Neurodegenerative diseases represent a very large group of heterogeneous disorders affecting specific subtypes of neurons in the brain. This book contributes insight both to the awareness of the brain and its neurodegenerative states. The chapters present current knowledge regarding genetics, molecular mechanisms, and new therapeutic strategies against neurodegenerative disorders. The book is intended to serve as a source to aid clinicians and researchers in the field, and also life science readers to increase their understanding and awareness of the clinical correlations, genetic aspects, neuropathological findings, and current therapeutic interventions in neurodegenerative diseases. I believe that this book will enlighten the curiosity for neurodegeneration and also encourage researchers to work on potentially effective molecular therapies for still mysterious neurodegenerative disorders.







Molecular Mechanism of Alzheimer's Disease


Book Description

Alzheimer’s disease (AD) is an age-related neurological disease that affects tens of millions of people, in addition to their carers. Hallmark features of AD include plaques composed of amyloid beta, as well as neurofibrillary tangles of tau protein. However, despite more than a century of study, the cause of Alzheimer’s disease remains unresolved. The roles of amyloid beta and tau are being questioned and other causes of AD are now under consideration. The contributions of researchers, model organisms, and various hypotheses will be examined in this Special Issue.




The American Psychiatric Association Practice Guideline on the Use of Antipsychotics to Treat Agitation or Psychosis in Patients With Dementia


Book Description

The guideline offers clear, concise, and actionable recommendation statements to help clinicians to incorporate recommendations into clinical practice, with the goal of improving quality of care. Each recommendation is given a rating that reflects the level of confidence that potential benefits of an intervention outweigh potential harms.




Insomnia and beyond - Exploring the therapeutic potential of orexin receptor antagonists


Book Description

Orexin/hypocretin neuropeptides, produced by a few thousand neurons in the lateral hypothalamus, are of critical importance for the control of vigilance and arousal of vertebrates, from fish to amphibians, birds and mammals. Two orexin peptides, called orexin-A and orexin-B, exist in mammals. They bind with different affinities to two distinct, widely distributed, excitatory G-protein- coupled receptors, orexin receptor type 1 and type 2 (OXR-1/2). The discovery of an OXR mutation causing canine narcolepsy, the narcolepsy-like phenotype of orexin peptide knockout mice, and the orexin neuron loss associated with human narcoleptic patients laid the foundation for the discovery of small molecule OXR antagonists as novel treatments for sleep disorders. Proof of concept studies from Glaxo Smith Kline, Actelion Pharmaceuticals Ltd. and Merck have now consistently demonstrated the efficacy of dual OXR antagonists (DORAs) in promoting sleep in rodents, dogs, non-human primates and humans. Some of these antagonists have completed late stage clinical testing in primary insomnia. Orexin drug discovery programs have also been initiated by other large pharmaceutical companies including Hoffmann La Roche, Novartis, Eli Lilly and Johnson & Johnson. Orexins are increasingly recognized for orchestrating the activity of the organism’s arousal system with appetite, reward and stress processing pathways. Therefore, in addition to models of insomnia, pharmacological effects of DORAs have begun to be investigated in rodent models of addiction, depression and anxiety. The first clinical trials in diabetic neuropathy, migraine and depression have been initiated with Merck’s MK-6096 (www.clinicaltrials.gov). Whereas the pharmacology of DORAs is established for their effects on wakefulness, pharmacological effects of selective OXR-1 or OXR-2 antagonists (SORAs) have remained less clear. From an evolutionary point of view, the OXR-2 was expressed first in most vertebrate lineages, whereas the OXR-1 is believed to result from a gene duplication event, when mammals emerged. Yet, both receptors do not have redundant function. Their brain expression pattern, their intracellular signaling, as well as their affinity for orexin-A and orexin-B differs. During the past decade most preclinical research on selective OXR-1 antagonism was performed with SB-334867. Only in recent years, other selective OXR-1 and OXR-2 antagonists with optimized selectivity profiles and pharmacokinetic properties have been discovered, and phenotypes of OXR-1 and OXR-2 knockout mice were described. The present Research Topic (referred to in the Editorial as “special topics issue”) comprises submissions of original research manuscripts as well as reviews, directed towards the neuropharmacology of OXR antagonists. The submissions are preclinical papers dealing with dual and/or selective OXR antagonists that shed light on the differential contribution of endogenous orexin signaling through both OXRs for cellular, physiological and behavioral processes. Some manuscripts also report on convergence or divergence of DORA vs. SORA effects with phenotypes expressed by OXR-1 or OXR-2 knockout animals. Ultimately these findings may help further define the potential of DORAs and SORAs in particular therapeutic areas in insomnia and beyond insomnia.




Cerebrospinal Fluid Biomarkers


Book Description

This volume covers the latest methods used in clinical neurochemistry laboratories for both clinical practice and research. Chapters in this book discuss topics such as techniques for cerebrospinal fluid (CSF) collection, pre-analytical processing, and basic CSF analysis; an examination of biomarkers including ELISA and automated immunochemical assays for amyloid and tau markers for Alzheimer’s disease; the analysis of neurofilaments by digital ELISA; and an example of successful novel immunoassay development. In the Neuromethods series style, chapters include the kind of detail and key advice from the specialists needed to get successful results in your laboratory. Cutting-edge and thorough, Cerebrospinal Fluid Biomarkers is a valuable resource for clinicians and researchers to use in CSF labs and CSF courses.




Alzheimer's Disease: Cellular and Molecular Aspects of Amyloid beta


Book Description

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.




Alzheimer's Disease: Biology, Biophysics And Computational Models


Book Description

Alzheimer's disease (AD) is the leading cause of dementia and, unfortunately, remains incurable. The social, emotional and financial implications of AD are immeasurable, and about 47 million people worldwide are affected by AD or other forms of dementia. As lifespans are improved by healthcare systems worldwide, age-associated neurodegenerative diseases are imposing an increasing challenge to science. It is becoming imperative for us to understand the causes of these diseases, AD in particular, at molecular and cellular levels. Starting with the broader picture from a biological perspective, this book takes the reader through fascinating dynamics within and outside of neurons in the brain.Alzheimer's Disease: Biology, Biophysics and Computational Models helps the reader to understand AD from mechanistic and biochemical perspectives at intra- and inter-cellular levels. It focuses on biochemical pathways and modeling associated with AD. Some of the recent research on biophysics and computational models related to AD are explained using context-driven computational and mathematical modeling and essential biology is discussed to understand the modeling research.