The amyloid precursor protein APP plays a key role in the pathogenesis of Alzheimer’s disease (AD), as proteolytical cleavage of APP gives rise to the Aβ peptide which is deposited in the brains of Alzheimer patients. Despite this, our knowledge of the normal cell biological and physiological functions of APP and the closely related APLPs is limited. This may have hampered our understanding of AD, since evidence has accumulated that not only the production of the Aβ peptide but also the loss of APP-mediated functions may contribute to AD pathogenesis. Thus, it appears timely and highly relevant to elucidate the functions of the APP gene family from the molecular level to their role in the intact organism, i.e. in the context of nervous system development, synapse formation and adult synapse function, as well as neural homeostasis and aging. Why is our understanding of the APP functions so limited? APP and the APLPs are multifunctional proteins that undergo complex proteolytical processing. They give rise to an almost bewildering array of different fragments that may each subserve specific functions. While Aβ is aggregation prone and neurotoxic, the large secreted ectodomain APPsα - produced in the non-amyloidogenic α-secretase pathway - has been shown to be neurotrophic, neuroprotective and relevant for synaptic plasticity, learning and memory. Recently, novel APP cleavage pathways and enzymes have been discovered that have gained much attention not only with respect to AD but also regarding their role in normal brain physiology. In addition to the various cleavage products, there is also solid evidence that APP family proteins mediate important functions as transmembrane cell surface molecules, most notably in synaptic adhesion and cell surface signaling. Elucidating in more detail the molecular mechanisms underlying these divers functions thus calls for an interdisciplinary approach ranging from the structural level to the analysis in model organisms. Thus, in this research topic of Frontiers we compile reviews and original studies, covering our current knowledge of the physiological functions of this intriguing and medically important protein family.

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.

This special topic issue of 'Neurodegenerative Diseases' contains contributions discussing the subject in-depth. 'Neurodegenerative Diseases' is a well-respected, international peer-reviewed journal in 'Neurobiology'. Special topic issues are included in the subscription.

The German version of this work has a long tradition, and this fourth edition is the first to see an English version. Its main feature is the international approach regarding both authors and topics. The four internationally renowned editors were able to acquire the leading specialists for each field as contributors to the book. No less than 120 authors, half of them from non-German speaking countries, ensure an extremely high standard and that cross-cultural aspects are considered. Another major feature is that the book presents the evidence such that it may be examined from at least four different entry points -- via basic disciplines of psychiatric knowledge about groups defined by demographic criteria. Detailed linkages to other chapters allow the inclusion of neighbouring disciplines, such as the neurosciences and molecular biology. Contemporary Psychiatry is also unique in including chapters on psychiatric disorders caused by catastrophes, disasters etc. -- aspects totally neglected by normal textbooks. While this book gives an overall view of the state of the art of psychiatric knowledge, it even goes so far as to suggest future perspectives.

Advanced Understanding of Neurodegenerative Diseases focuses on different types of diseases, including Alzheimer's disease, frontotemporal dementia, different tauopathies, Parkinson's disease, prion disease, motor neuron diseases such as multiple sclerosis and spinal muscular atrophy. This book provides a clear explanation of different neurodegenerative diseases with new concepts of understand the etiology, pathological mechanisms, drug screening methodology and new therapeutic interventions. Other chapters discuss how hormones and health food supplements affect disease progression of neurodegenerative diseases. From a more technical point of view, some chapters deal with the aggregation of prion proteins in prion diseases. An additional chapter to discuss application of stem cells. This book is suitable for different readers: college students can use it as a textbook; researchers in academic institutions and pharmaceutical companies can take it as updated research information; health care professionals can take it as a reference book, even patients' families, relatives and friends can take it as a good basis to understand neurodegenerative diseases.

This book highlights the key phases and central findings of Alzheimer’s Disease research since the introduction of the label ‘Alzheimer’s Disease’ in 1910. The author, Christian Behl, puts dementia research in the context of the respective zeitgeist and summarizes the paths that have led to the currently available Alzheimer’s drugs. As the reader is taken through the major developments in Alzheimer's Disease research, particularly over the past thirty years, Behl poses critical questions: Why are the exact causes of Alzheimer's Disease still in the dark, despite all the immense, worldwide research efforts in academia as well as in the pharmaceutical industry? Why has the majority of an entire research field kept focusing on a single hypothesis that establishes the deposition of the amyloid beta peptide in the brain as the key trigger of Alzheimer's pathology, even though this concept has still not been convincingly proven in the clinics? Are there other hypotheses that might explain the pathogenesis of this complex brain disease, and if so, why were these perspectives not adequately followed? In this book, Behl tries to answer these questions. Starting with the historical background, the author illustrates the long and arduous research journey, its numerous setbacks, and the many alternative explanations for the disease, which have started gaining increasing attention and acceptance in the Alzheimer’s research community only more recently. With his deep dive into the history and progression of this research, including the most recent developments, Behl explains why he believes that it is high time to promote a paradigm shift in Alzheimer’s Disease research. The book is written for all researchers in the fields of neurobiology and neurodegeneration, as well as other biomedical fields, who would like to gain a broad and beyond the surface insight into (the key developments of) one of the most promoted research fields of our time. With its extensive literature references and over 100 illustrations, the book is also attractive for students and interested lay persons. Elaborating on all the different aspects and research approaches of this research field, the author aims to convince the reader that the underlying causes of Alzheimer’s Disease may be much more complex than previously thought and that this must be considered for future research directions. While he hopes that the Alzheimer’s research community is finally ready to shed its ‘amyloid-straitjacket’ that has hampered progress for too long, he is also convinced that a much-needed paradigm shift can guide future Alzheimer’s Disease research and provide a new and broader perspective on this age-dependent brain disease.

Alzheimer's disease (AD), the most common form of neurodegenerative disorder in the elderly, is characterised pathologically by extracellular amyloid plaques and intracellular neurofibrillary tangles, pathophysiologically by synaptic dysfunction, and clinically by a progressive decline in cognition. Currently, AD has no cure and its prevalence is predicted to triple by 2050 with the rapid increase in the ageing population, unless more effective treatments are developed. Since the publication of the second book volume, the rapid progress in the research fields of AD and dementia continues through the intensive efforts of research scientists worldwide. This third book volume contains 15 chapters, bringing together a presentation of research frontiers in current AD/dementia research. The topics include molecular genetics of AD, gene expression abnormalities in AD progression, presenilins, taupathy in AD, single -induced(neuron gene expression abnormalities in AD, intracellular A neurodegeneration, roles of lipoprotein receptors in AD onset and progression, cholesterol and tau hyperphosphorylation, AD diagnostics and therapeutic strategies, in vivo visualisation of amyloid-like structures, cathepsin B, antiamyloidogenesis and neuroprotection, environmental enrichment, Fragile X mental retardation gene and dementia, category learning in Parkinson's disease, cerebrovascular disease and dementia, and dementia and hypertension. These chapters cover current advances in our understanding of the pathogenic mechanisms underlying AD and dementia, in the diagnosis of early AD and dementia, and in the development of therapeutic agents that target memory-relevant AD pathogenesis. The book will be highly valuable to students and scientists worldwide who are interested in the scientific research progress in AD and dementia.