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Alzheimer’s Disease (AD) is the product of the slow and progressive degenerative alteration that develops in the adult brain and can remain asymptomatic for a considerable time before cognitive deficits becomes evident. The main challenge for researchers is to identify markers of this degenerative process, and, in this sense, data has been generated through experiments bringing to light new mechanisms and hypothesis to explain its pathophysiology. This book is a review of recent studies in AD molecular biology. Chapters explain various facets of AD, which include animal models, morphological changes, membrane composition, amyloidogenic peptides, intracellular transport systems, and the role of oxidative stress and calcium deregulation. Readers will understand the molecular mechanisms behind AD and therefore broaden their perspective on this neurodegenerative disease and its progression.
Animals have been used to model diseases or test new treatments since around 300 BC, and undoubtedly our ability to model disease in animals – including transgenic animals – has provided major breakthroughs in all fields of biomedical research. Due to their complexity and plurality of pathology and symptomatology, the study of neurodegenerative diseases relies heavily on animal models. These models have been developed in many species in the attempt to undercover the complex nature of the disease mechanisms involved. The ultimate goal is to test promising therapies and to manage, prevent or cure neurodegenerative disease. But because most animal models in this area do not reproduce the full phenotypical disease spectrum and the etiology and clinical presentation of neurodegenerative diseases differ from one patient to the next, the testing of these diseases in animal models often translates poorly to indices of efficacy when applied to the clinical population. Written by experts in the field with these advances and challenges in mind, this handbook provides an updated overview of the animal models being developed and used to study complex disease dynamics. The first part of the book presents an overview of animal models of various species and includes a review of new invertebrate animal models to study neurodegeneration. The second section presents the use of animal models to pinpoint disease mechanisms, and the last part of the handbook examines the various therapeutic interventions being used in models of neurodegenerative disease.
Although age has been recognized as a risk factor for late-onset dementia of Alzheimer type, its etiology is unknown as yet. Several age-related metabolic abnormalities may thus become important for the pathogenesis of the late-onset form. Studies at the cellular/molecular level in brain tissue are possible post mortem, but lack information on the beginning of the disorder. In this supplement, different approaches are dealt with how to induce structural and/or metabolic abnormalities in relevant cell cultures, in brain slices and in experimental animals, and how behavioral changes parallel the metabolic variations.
Alzheimer’s disease (AD) is a major and increasing burden on families, communities, and national health budgets. Despite intensive and extended research, there is still widespread debate about its cause(s), and no effective treatments exist. Familial (inherited, mainly early onset) and sporadic (mainly late onset) forms of the disease exist, and it is uncertain to what extent they are related. Transgenic mouse models have dominated the investigation of this disease, but their validity can be questioned. Numerous alternative models exist that can provide valuable information on the molecular and cellular basis of AD. In this chapter, we review the various invertebrate, nonmammalian vertebrate, and mammalian models and how these have been used to investigate this disease. We examine the strengths and weaknesses of these various model systems. Of course, animal models never completely reflect the true nature of a human disease, but progress in understanding and finding preventative and ameliorative treatments for AD is hindered by the lack of a convincing hypothesis for the cause of this complex condition.
Highlighting the latest and the most timely aspects of Alzheimer's disease research, this text will enable scientists in related research fields, as well as physicians working with Alzheimer's disease patients, to obtain a quick and complete overview of the current state of the art in one of the most exciting fields in neuroscience research. Leading scientists have contributed articles focusing on key developments in this field. This includes an overview about the pathology, the genetics of familial Alzheimer's disease, proteolytic generation and aggregation of amyloid -peptide, presenilins, risk factors such as ApoE, and transgenic animal models. Some of the latest developments in Alzheimer's disease research, including the effect of presenilin knock outs on amyloid -peptide generation, are also included.
In recent years, medical developments have resulted in an increase in human life expectancy. The editors have extensive knowledge and experience in this field and the book is aimed at undergraduates, postgraduates, and academics. The chapters cover Alzheimer's disease, Parkinson's disease, Huntington's, and other neurodegenerative disorders.
Alzheimer's Disease Research Guide: Animal Models for Understanding Mechanisms and Medications provides researchers with a comprehensive guide, detailing every aspect of Alzheimer's Disease research, including chapters on neuroinflammation, immunotherapy, biomarkers, and animal modeling. This book begins with historical perspectives of both pathological chronology and pathological biochemistry in relation to Alzheimer’s disease. Other chapters review Amyloidogenic AB and Non-Amyloidogenic tau and Metabolism of AB major components to the research and understanding of Alzheimer’s research. The book concludes with specific treatment chapters including how to develop safe, effective, and inexpensive medications and the application of genome editing to the treatment of Familial Alzheimer's Disease. Written by world renowned expert in Alzheimer’s research, this book is a valuable resource for all researchers. Reviews why familial Alzheimer’s disease is vital to understanding sporadic Alzheimer’s disease Describes the latest “game changer” animal models of Alzheimer's disease and frontotemporal dementia in detail Explains how various Alzheimer’s disease medications have failed clinical trials Discusses pros and cons of therapeutic antibodies, lecanemab and donanemab, that were recently found to be effective in recent clinical trials Details the application of genome editing as a treatment for familial Alzheimer’s disease Proposes publishing “Journal of Negative Data” for the days of generative AI-assisted publication, AI being unable to distinguish between reproducible and unreproducible data, particularly important in Alzheimer’s research
The Molecular and Cellular Basis of Neurodegenerative Diseases: Underlying Mechanisms presents the pathology, genetics, biochemistry and cell biology of the major human neurodegenerative diseases, including Alzheimer’s, Parkinson’s, frontotemporal dementia, ALS, Huntington’s, and prion diseases. Edited and authored by internationally recognized leaders in the field, the book's chapters explore their pathogenic commonalities and differences, also including discussions of animal models and prospects for therapeutics. Diseases are presented first, with common mechanisms later. Individual chapters discuss each major neurodegenerative disease, integrating this information to offer multiple molecular and cellular mechanisms that diseases may have in common. This book provides readers with a timely update on this rapidly advancing area of investigation, presenting an invaluable resource for researchers in the field. Covers the spectrum of neurodegenerative diseases and their complex genetic, pathological, biochemical and cellular features Focuses on leading hypotheses regarding the biochemical and cellular dysfunctions that cause neurodegeneration Details features, advantages and limitations of animal models, as well as prospects for therapeutic development Authored by internationally recognized leaders in the field Includes illustrations that help clarify and consolidate complex concepts