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.

Klappentext

A panel of highly skilled investigators describe in detail their state-of-the-art biochemical, cell biological, and molecular biological techniques for studying the molecular basis of Alzheimer's disease. These readily reproducible, step-by-step methods focus on work with the amyloid precursor protein and the amyloidogenic peptide Aß, but also include-with the recent identification of presenilin proteins-techniques for determining the structure and biological function of these proteins. In addition, there are chapters covering the tau protein and its role in Alzheimer's disease, as well as an introductory discussion of the history of the disease, its genetic basis, and the currently available and possible future therapeutic agents. Cutting-edge and wide ranging, Alzheimer's Disease: Methods and Protocols provides ready access to proven, reproducible methods for elucidating the molecular basis of this most common senile dementia.

Zusammenfassung
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.

Inhalt
to Alzheimer's Disease.- The Genetics of Alzheimer's Disease.- Advances in Methodology and Current Prospects for Primary Drug Therapies for Alzheimer's Disease.- Production and Functional Assays of Recombinant Secreted Amyloid Precursor Protein (APP) (sAPP?).- Quantifying A?140 and A?142 Using Sandwich-ELISA.- Electrophoretic Separation and Immunoblotting of A?140 and A?142.- A?-Induced Proinflammatory Cytokine Release from Differentiated Human THP-1 Monocytes.- Effects of the ?-Amyloid Peptide on Membrane Ion Permeability.- Analysis of ?-Amyloid Peptide Degradation In Vitro.- Posttranslational Modifications of Amyloid Precursor Protein.- Posttranslational Modifications of the Amyloid Precursor Protein.- Using an Amyloid Precursor Protein (APP) Reporter to Characterize ?-Secretase.- Inhibition of ?-Secretase by Zinc Metalloproteinase Inhibitors.- Development of Neoepitope Antibodies Against the ?-Secretase Cleavage Site in the Amyloid Precursor Protein.- ?-Secretase.- Using ?-Secretase Inhibitors to Distiguish the Generation of the A? Peptides Terminating at Val-40 and Ala-42.- Designing Animal Models of Alzheimer's Disease with Amyloid Precursor Protein (APP) Transgenes.- Phosphorylation of Amyloid Precursor Protein (APP) Family Proteins.- Determining the Transmembrane Topology of the Presenilins.- Normal Proteolytic Processing of the Presenilins.- Apoptotic Proteolytic Cleavage of the Presenilins by Caspases.- The Phosphorylation of Presenilin Proteins.- Interaction of the Presenilins with the Amyloid Precursor Protein (APP).- Distribution of Presenilins and Amyloid Precursor Protein (APP) in Detergent-Insoluble Membrane Domains.- Characterization and Use of Monoclonal Antibodies to Tau and Paired Helical Filament Tau.- Tau PhosphorylationBoth In Vitro and in Cells.- Transglutaminase-Catalyzed Formation of Alzheimer-Like Insoluble Complexes from Recombinant Tau.