This volume of the Subcellular Biochemistry series is the result of the long-standing research interest of the editor in the molecular mechanism underlying Alzheimer’s disease and other amyloid diseases, indicated also by the earlier book in the series (Volume 38), devoted to Alzheimer’s disease. The broad coverage within the present amyloidogenesis book represents an attempt to collate current knowledge relating to the proteins and peptides involved in most of the known amyloid diseases, together with some amyloid/fibril-forming proteins and peptides that are not involved in diseases. Thus, the range of topics included is comprehensive and furthermore it was thought appropriate to include both basic science and clinical presentation of the subjects under discussion.

Research indicates that most neurodegenerative diseases, systemic amyloidoses and many others, arise from the misfolding and aggregation of an underlying protein. This is the first book to discuss significant achievements in protein structure-function relationships in biochemistry, molecular biology and molecular medicine. The authors summarize recent progress in the understanding of the relationships between protein misfolding, aggregation and development of protein deposition disorders.

This book collects papers by biology, chemistry and physics researchers all actively working in the field of protein aggregation as related to amyloid diseases. Protein precipitates having a highly ordered, fibril-like structure accompany several fatal diseases, such as Alzheimer's, Parkinson's, Creutzfeldt-Jacob and Huntington diseases. Amyloid fibrils associated to different diseases share a common cross beta repeat structure, despite the lack of sequence homologies and structure similarities in the relative proteins. About 20 proteins are known to form amyloid fibrils under physiological conditions. In any of them a conformational change into an unfolding intermediate seems to be responsible for amyloid fibrils formation. A growing body of evidence indicates that in vitro any protein or polypeptide can assembly into fibrillar structures under mildly denaturing conditions, where metastable unfolding intermediates become stabilized. These findings have added further interest to the outstanding problem of protein folding/unfolding and aggregation, whose high interdisciplinary character touches upon biology, chemistry and physics. Indeed, only by joining different expertise we may hope to achieve a unifying view of protein aggregation mechanism in terms of a few general principles. A central issue in the problem of amyloid formation is the understanding of the thermodynamic transitions governing this type of self-organization process in which the symmetry of the interacting molecules should play a relevant role. The first paper of this volume by Manno deals with the modeling of amyloid formation in the frame of physics of colloidal coagulation, and highlights those theoretical aspects that can be investigated by experiments in vitro. The relevance of crowding and confinement, or a combination of them, on the aggregation of proteins in living system is discussed in the paper of Temussi, where results obtained from studies in vitro and in vivo are revised and compared. The paper by Higuchi et al. addresses the theme of disease transmission in living organisms. The authors present the case of systemic amyloidosis in mice showing that pre-formed amyloid fibrils injected in, or ingested by, mice susceptible to infection are capable to accelerate amyloid deposition. A new emerging hypothesis on the onset of amyloid diseases points out the role played by small oligomeric species representing early pre-fibrillar intermediates. Such small aggregates have been observed in the case of beta-peptide responsible for Alzheimer disease. The paper by Di Carlo et al. describes the toxic properties of beta-peptide aggregates with different size, and indicates the possible degeneration pathways leading to the disease. If pre-fibrillar small oligomers are amyloid intermediates, inhibiting their formation should be an important target for therapeutic strategies. The paper by Sgarbossa et al. illustrates the potential use of small polycyclic aromatic molecules that can act as fibrillogenesis inhibitors by imposing unfavorable conformational constraints to the aggregating molecules. The paper by Pastore discusses the aggregation properties of proteins having homo-polymeric stretches, whose tract length determines the onset of the pathologies. The most famous of them is the Huntington disease associated to expansion of polyglutamine repeat. Bisaglia et al. revised the case of alpha-synuclein involved in Parkinson disease. The paper describes the capacity of this protein of adopting different conformations as a response to the environments, with relation to its physiological function or possible pathological role. Finally, two papers concern the role of metal ions on protein aggregation. The paper by Morante gives a review of the possible harmful or useful effects of some metal ions on two pathological proteins, examined through the synergic use of computational and experimental techniques. The paper by Militello et al. describes metal effects on the conformational change and structural properties of aggregates of beta-lactoglobulin and bovine serum albumin, taken as convenient model systems for studying protein aggregation. We thank the contributing authors for having provide altogether a wide perspective, multi-faceted survey of the conceptual and experimental tools that can be applied for unraveling the mechanism of protein aggregation.

A proven collection of readily reproducible techniques for studying amyloid proteins and their involvement in the etiology, pathogenesis, diagnosis, and therapy of amyloid diseases. The contributors provide methods for the preparation of amyloid and its precursors (oligomers and protofibrils), in vitro assays and analytical techniques for their study, and cell culture models and assays for the production of amyloid proteins. Additional chapters present readily reproducible techniques for amyloid extraction from tissue, its detection in vitro and in vivo, as well as nontransgenic methods for developing amyloid mouse models. The protocols follow the successful Methods in Molecular BiologyTM series format, each offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls.

The second edition of this text presents an overview of the most recent developments in this area including clinical presentation, etiology, pathogenesis, and differential diagnosis. The rationale for various therapies, including transplantation, is discussed and tissue diagnosis (its pitfalls and strategies for avoiding them) and laboratory support are included. The involvement of all major organ systems including renal/genitourinary, cardiac, gastrointestinal, pulmonary, peripheral nerve/central nervous system, soft tissue, skin, lymph node/spleen and bone marrow pathology is also covered. Amyloid and Related Disorders, Second Edition will be invaluable to specialized and general pathologists as well as cytopathologists. Other medical professionals may also benefit from this concise update on the systemic amyloidoses.

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.

Advances in Clinical Chemistry, Volume 99, the latest installment in this internationally acclaimed series, contains chapters authored by world-renowned clinical laboratory scientists, physicians and research scientists. The serial discusses the latest and most up-to-date technologies related to the field of clinical chemistry, with this release including chapters on Extracellular vesicle associated proteins as potential biomarkers, Molecular and non-molecular approaches to etiologic diagnosis of gastroenteritis, Circular RNAs and cancer: Opportunities and challenges, Mass spectrometry-based metabolomics for an in-depth questioning of human health, Application of microfluidic technology in cancer research and therapy, Advances in aptasensor technology, and much more. Covers the most up-to-date technologies in clinical chemistry and clinical laboratory science Authored by world renowned clinical laboratory scientists, physicians and research scientists Provides the international benchmark for novel analytical approaches in the clinical laboratory