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.

InhaltsangabeIntroduction to Alzheimer's Disease, David Allsop. The Genetics of Alzheimer's Disease, Nick Brindle and Peter St. George-Hyslop. Advances in Methodology and Current Prospects for Primary Drug Therapies for Alzheimer's Disease, David S. Knopman. Production and Functional Assays of Recombinant Secreted Amyloid Precursor Protein (APP) (sAPPa), Steven W. Barger. Quantifying Ab1-40 and Ab1-42 Using Sandwich-ELISA, Daniel M. Skovronsky, Jun Wang, Virginia M.-Y. Lee, and Robert W. Doms. Electrophoretic Separation and Immunoblotting of Ab1-40 and Ab1-42 Matthias Staufenbiel and Paolo A. Paganetti. Ab-Induced Proinflammatory Cytokine Release from Differentiated Human THP-1 Monocytes, Kurt R. Brunden, June Kocsis-Angle, Paula Embury, and Stephen L. Yates. Effects of the b-Amyloid Peptide on Membrane Ion Permeability, Hugh A. Pearson. Analysis of b-Amyloid Peptide Degradation In Vitro, Barbara Cordell and Asha Naidu. Posttranslational Modifications of the Amyloid Precursor Protein: Ectodomain Phosphorylation and Sulfation, Jochen Walter and Christian Haass. Posttranslational Modifications of the Amyloid Precursor Protein: Glycosylation, Chen Liu, Tomasz Rozmyslowicz, Magda Stwora-Wojczyk, Boguslaw Wojczyk, and Steven L. Spitalnik. Using an Amyloid Precursor Protein (APP) Reporter to Characterize a-Secretase, Susan Boseman Roberts. Inhibition of a-Secretase by Zinc Metalloproteinase Inhibitors, S. Parvathy, Anthony J. Turner, and Nigel M. Hooper. Development of Neoepitope Antibodies Against the b-Secretase Cleavage Site in the Amyloid Precursor Protein Carol W. Gray and Eric H. Karran. b-Secretase: Tissue Culture Studies of Sequence Specificity, Inhibitors, and Candidate Enzymes, Martin Citron. Using g-Secretase Inhibitors to Distiguish the Generation of the Ab Peptides Terminating at Val-40 and Ala-42, Paolo A. Paganetti and Matthia Staufenbiel. Designing Animal Models of Alzheimer's Disease with Amyloid Precursor Protein (APP) Transgenes, Jeanne F. Loring. Phosphorylation ofAmyloid Precursor Protein (APP) Family Proteins, Toshiharu Suzuki, Kanae Ando, Ko-ichi Iijima, Shinobu Oguchi, and Shizu Takeda. Determining the Transmembrane Topology of the Presenilins, Gopal Thinakaran and Andrew Doan. Normal Proteolytic Processing of the Presenilins, Henrike Hartmann and Bruce A. Yankner. Apoptotic Proteolytic Cleavage of the Presenilins by Caspases, Tae-Wan Kim. The Phosphorylation of Presenilin Proteins, Jochen Walter. Interaction of the Presenilins with the Amyloid Precursor Protein (APP), Andreas Weidemann, Krzysztof Paliga, Ulrike Dürrwang, Friedrich Reinhard, Dai Zhang, Rupert Sandbrink, Geneviève Evin, Colin L. Masters, and Konrad Beyreuther. Distribution of Presenilins and Amyloid Precursor Protein (APP) in Detergent-Insoluble Membrane Domains, Edward T. Parkin, Anthony J. Turner and Nigel M. Hooper. Characterization and Use of Monoclonal Antibodies to Tau and Paired Helical Filament Tau, Peter Davies. Tau Phosphorylation Both In Vitro and in Cells. C. Hugh Reynolds, Graham M. Gibb, and Simon Lovestone. Transglutaminase-Catalyzed Formation of Alzheimer-Like Insoluble Complexes from Recombinant Tau, Brian J. Balin and Denah M. Appelt. Index.

Introduction to Alzheimer''s Disease, David Allsop. The Genetics of Alzheimer''s Disease, Nick Brindle and Peter St. George-Hyslop. Advances in Methodology and Current Prospects for Primary Drug Therapies for Alzheimer''s Disease, David S. Knopman. Production and Functional Assays of Recombinant Secreted Amyloid Precursor Protein (APP) (sAPPa), Steven W. Barger. Quantifying Ab1-40 and Ab1-42 Using Sandwich-ELISA, Daniel M. Skovronsky, Jun Wang, Virginia M.-Y. Lee, and Robert W. Doms. Electrophoretic Separation and Immunoblotting of Ab1-40 and Ab1-42 Matthias Staufenbiel and Paolo A. Paganetti. Ab-Induced Proinflammatory Cytokine Release from Differentiated Human THP-1 Monocytes, Kurt R. Brunden, June Kocsis-Angle, Paula Embury, and Stephen L. Yates. Effects of the b-Amyloid Peptide on Membrane Ion Permeability, Hugh A. Pearson. Analysis of b-Amyloid Peptide Degradation In Vitro, Barbara Cordell and Asha Naidu. Posttranslational Modifications of the Amyloid Precursor Protein: Ectodomain Phosphorylation and Sulfation, Jochen Walter and Christian Haass. Posttranslational Modifications of the Amyloid Precursor Protein: Glycosylation, Chen Liu, Tomasz Rozmyslowicz, Magda Stwora-Wojczyk, Boguslaw Wojczyk, and Steven L. Spitalnik. Using an Amyloid Precursor Protein (APP) Reporter to Characterize a-Secretase, Susan Boseman Roberts. Inhibition of a-Secretase by Zinc Metalloproteinase Inhibitors, S. Parvathy, Anthony J. Turner, and Nigel M. Hooper. Development of Neoepitope Antibodies Against the b-Secretase Cleavage Site in the Amyloid Precursor Protein Carol W. Gray and Eric H. Karran. b-Secretase: Tissue Culture Studies of Sequence Specificity, Inhibitors, and Candidate Enzymes, Martin Citron. Using g-Secretase Inhibitors to Distiguish the Generation of the Ab Peptides Terminating at Val-40 and Ala-42, Paolo A. Paganetti and Matthia Staufenbiel. Designing Animal Models of Alzheimer''s Disease with Amyloid Precursor Protein (APP) Transgenes, Jeanne F. Loring. Phosphorylation of Amyloid Precursor Protein (APP) Family Proteins, Toshiharu Suzuki, Kanae Ando, Ko-ichi Iijima, Shinobu Oguchi, and Shizu Takeda. Determining the Transmembrane Topology of the Presenilins, Gopal Thinakaran and Andrew Doan. Normal Proteolytic Processing of the Presenilins, Henrike Hartmann and Bruce A. Yankner. Apoptotic Proteolytic Cleavage of the Presenilins by Caspases, Tae-Wan Kim. The Phosphorylation of Presenilin Proteins, Jochen Walter. Interaction of the Presenilins with the Amyloid Precursor Protein (APP), Andreas Weidemann, Krzysztof Paliga, Ulrike Dürrwang, Friedrich Reinhard, Dai Zhang, Rupert Sandbrink, Genevieve Evin, Colin L. Masters, and Konrad Beyreuther. Distribution of Presenilins and Amyloid Precursor Protein (APP) in Detergent-Insoluble Membrane Domains, Edward T. Parkin, Anthony J. Turner and Nigel M. Hooper. Characterization and Use of Monoclonal Antibodies to Tau and Paired Helical Filament Tau, Peter Davies. Tau Phosphorylation Both In Vitro and in Cells. C. Hugh Reynolds, Graham M. Gibb, and Simon Lovestone. Transglutaminase-Catalyzed Formation of Alzheimer-Like Insoluble Complexes from Recombinant Tau, Brian J. Balin and Denah M. Appelt. Index.