methods in molecular biology978-1-4939-7816...institute of physical chemistry “rocasolano”...
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ME T H O D S I N MO L E C U L A R B I O L O G Y
Series EditorJohn M. Walker
School of Life and Medical SciencesUniversity of Hertfordshire
Hatfield, Hertfordshire, AL10 9AB, UK
For further volumes:http://www.springer.com/series/7651
Amyloid Proteins
Methods and Protocols
Third Edition
Edited by
Einar M. Sigurdsson
Department of Neuroscience and Physiology, New York University School of Medicine, New YorkUniversity Langone Health, New York, NY, USA; Department of Psychiatry, New York University
School of Medicine, New York University Langone Health, New York, NY, USA
Miguel Calero
Chronic Disease Programme-CROSADIS, CIBERNED, Queen Sofia Foundation Alzheimer Center, CIENFoundation, Instituto de Salud Carlos III, Madrid, Spain
María Gasset
Institute of Physical Chemistry “Rocasolano”, Spanish National Research Council (CSIC), Madrid, Spain
EditorsEinar M. SigurdssonDepartment of Neuroscienceand PhysiologyNew York University Schoolof MedicineNew York University LangoneHealthNew York, NY, USA
Department of PsychiatryNew York University Schoolof MedicineNew York University LangoneHealthNew York, NY, USA
Miguel CaleroChronic Disease Programme-CROSADISCIBERNED, Queen Sofia FoundationAlzheimer CenterCIEN Foundation, Instituto deSalud Carlos IIIMadrid, Spain
Marıa GassetInstitute of Physical Chemistry “Rocasolano”Spanish National Research Council (CSIC)Madrid, Spain
ISSN 1064-3745 ISSN 1940-6029 (electronic)Methods in Molecular BiologyISBN 978-1-4939-7815-1 ISBN 978-1-4939-7816-8 (eBook)https://doi.org/10.1007/978-1-4939-7816-8
Library of Congress Control Number: 2018942014
© Springer Science+Business Media, LLC, part of Springer Nature 2018This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material isconcerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproductionon microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation,computer software, or by similar or dissimilar methodology now known or hereafter developed.The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply,even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulationsand therefore free for general use.The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed tobe true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty,express or implied, with respect to the material contained herein or for any errors or omissions that may have been made.The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Cover Caption: The cover art depicts ATTR amyloid deposits as detailed in Chapter 24 by Westermark et al.
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Preface
Amyloid diseases are characterized by the deposition of insoluble fibrous amyloid proteins.The word “amyloid” indicates a starch-like compound and, though a misnomer, continuesto be the accepted term for this group of protein conformational disorders. Approximately30 different proteins can form amyloid and although there is usually no homology in theiramino acid sequence, all share a β-pleated sheet as the polymer scaffold. Historically, theseβ-pleated deposits were detected by histological dyes, and the characteristic fibril structureconfirmed with electron microscopy. As these amyloids were purified and sequenced, variousin vitro techniques were developed, often using synthetic peptides or highly purifiedamyloids derived from diseased tissue. Development of animal models occurred concur-rently and some of these diseases can now be passed on to animals by injecting them withamyloid-rich tissue fractions, or shown to spread between cells in vivo or in culture,suggesting a transmissible nature of these protein polymers. However, for most amyloi-doses, transgenic technology has been necessary for recapitulating the disease but its severitycan be enhanced by amyloid seeding. Together, these in vitro and in vivo models have beenused to understand the etiology and pathogenesis of amyloid diseases as well as to screen fordrugs to prevent the formation of and/or clear these aggregates.
Several of these methods and protocols are detailed in this third edition of AmyloidProteins: Methods and Protocols, using examples from various amyloids. Substantial changeshave been made from the second edition of this volume. Several classic methods/protocolsthat did not warrant updates are not included in the third edition. Importantly, numerousnew chapters have been added that cover new techniques and topics not addressed in thesecond edition. The volume is divided into three parts. Part I contains in vitro assays thatfocus on preparation of various amyloids and their precursors or detail specific analyticalmethods for studying these peptides and proteins. Part II describes cell culture models andassays for production of amyloid proteins, and Part III consists of protocols for amyloidextraction from tissue, its detection and characterization in vitro and in vivo, and assays thatare modulated by amyloids. Most of the chapters follow a similar format and are detailedprotocols for performing a particular procedure. However, certain chapters focus more ongeneral principles and theoretical issues of a particular method.
It is our hope that these articles will be useful both for students and scientists new to theamyloid field, as well as for seasoned investigators learning new techniques to further theirresearch.
We would like to thank the authors for their contribution and the series editor, Dr. JohnM. Walker, for the opportunity to edit this book.
New York, NY, USA Einar M. SigurdssonMadrid, Spain Miguel CaleroMadrid, Spain Marıa Gasset
v
Contents
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vContributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
PART I IN VITRO MODELS AND ASSAYS
1 Preparation of Pure Populations of Amyloid β-Protein Oligomersof Defined Size . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3Eric Y. Hayden, Joseph L. Conovaloff, Ashley Mason, Gal Bitan,and David B. Teplow
2 Preparation of a Well-Defined and Stable β-Barrel Pore-FormingAβ42 Oligomer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13Montserrat Serra-Batiste, Martı Ninot-Pedrosa, Eduard Puig,Sonia Ciudad, Margarida Gairı, and Natalia Carulla
3 Unveiling Brain Aβ Heterogeneity Through TargetedProteomic Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23Agueda Rostagno, Thomas A. Neubert, and Jorge Ghiso
4 Preparation of α-Synuclein Amyloid Assemblies for ToxicityExperiments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45Serene W. Chen and Nunilo Cremades
5 Generation and Characterization of Stable α-Synuclein Oligomers . . . . . . . . . . . . 61Leire Almandoz-Gil, Martin Ingelsson, and Joakim Bergstrom
6 In Vitro Analysis of α-Synuclein Amyloid Formationand Cross-Reactivity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73Istvan Horvath, Sandra Rocha, and Pernilla Wittung-Stafshede
7 Preparation of Tau Oligomers After the Protein Extractionfrom Bacteria and Brain Cortices. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85Elentina K. Argyrousi, Agnieszka Staniszewski, Russell E. Nicholls,and Ottavio Arancio
8 Purification and Characterization of Low-n Tau Oligomers . . . . . . . . . . . . . . . . . . 99Senthilvelrajan Kaniyappan, Ram Reddy Chandupatla,and Eckhard Mandelkow
9 Preparation and Characterization of Tau Oligomer Strains . . . . . . . . . . . . . . . . . . . 113Urmi Sengupta, Mariana Carretero-Murillo, and Rakez Kayed
10 Purification and Fibrillation of Recombinant Human Amyloid-β,Prion Protein, and Tau Under Native Conditions. . . . . . . . . . . . . . . . . . . . . . . . . . . 147Alexander Sandberg and Sofie Nystrom
11 Preparation of Amyloidogenic Aggregates from EF-Handβ-Parvalbumin and S100 Proteins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167Javier Martınez, Joana S. Crist�ovao, Rosa Sanchez, Maria Gasset,and Claudio M. Gomes
vii
12 Kinetic Analysis of Amyloid Formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181Georg Meisl, Thomas C. T. Michaels, Sara Linse, and Tuomas P. J. Knowles
13 Mapping Amyloid Regions in Gad m 1 with Peptide Arrays . . . . . . . . . . . . . . . . . . 197Rosa Sanchez, Javier Martınez, Laura Montoya, Milagros Castellanos,and Maria Gasset
14 Noninvasive Structural Analysis of Intermediate Species DuringFibrillation: An Application of Small-Angle X-Ray Scattering . . . . . . . . . . . . . . . . . 209Annette Eva Langkilde, Fatima Herranz-Trillo, Pau Bernad�o,and Bente Vestergaard
15 Analysis of Covalent Modifications of Amyloidogenic Proteins UsingTwo-Dimensional Electrophoresis: Prion Protein and Its Sialylation . . . . . . . . . . 241Elizaveta Katorcha and Ilia V. Baskakov
16 Amplification and Detection of Minuscule Amounts of MisfoldedPrion Protein by Using the Real-Time Quaking-Induced Conversion . . . . . . . . . 257Matthias Schmitz, Niccolo Candelise, Franc Llorens, and Inga Zerr
PART II CELL CULTURE MODELS AND ASSAYS
17 Bacterial Amyloids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267Margery L. Evans, Elizabeth Gichana, Yizhou Zhou,and Matthew R. Chapman
18 Addressing Intracellular Amyloidosis in Bacteria with RepA-WH1,a Prion-Like Protein . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289Laura Molina-Garcıa, Fatima Gasset-Rosa, Marıa Moreno-del Alamo,Susana Moreno-Dıaz de la Espina, and Rafael Giraldo
19 Study of Amyloids Using Yeast . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313Reed B. Wickner, Dmitry Kryndushkin, Frank Shewmaker,Ryan McGlinchey, and Herman K. Edskes
20 Neurotoxic Ca2+ Signaling Induced by Amyloid–β Oligomersin Aged Hippocampal Neurons In Vitro . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341Lucıa Nunez, Marıa Calvo-Rodrıguez, Erica Caballero,M�onica Garcıa-Durillo, and Carlos Villalobos
21 Preparation and Culturing of Human Primary Vascular Cells . . . . . . . . . . . . . . . . . 355Finnbogi R. Thormodsson, Ingvar H. Olafsson, and Dadi Th. Vilhjalmsson
22 Live Imaging of Pathological Tau Protein and Tau Antibodiesin a Neuron-Like Cellular Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371Dov B. Shamir, Yan Deng, and Einar M. Sigurdsson
23 Effects of Amyloid-β Peptide on the Biology of HumanNeural Stem Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381Adela Bernabeu-Zornoza, Raquel Coronel, Marıa Lachgar,Charlotte Palmer, and Isabel Liste
viii Contents
PART III IN VIVO MODELS AND ASSAYS
24 Development of Mouse Monoclonal Antibodies Against HumanAmyloid Fibril Proteins for Diagnostic and Research Purposes . . . . . . . . . . . . . . . 401Gunilla T. Westermark, Elisabet Ihse, and Per Westermark
25 Identification and Characterization of Amyloid-β Accumulationin Synaptic Mitochondria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415Shi Fang Yan, Firoz Akhter, Alexander A. Sosunov, and Shirley ShiDu Yan
26 Biochemical Properties of Pathology-Related Tau Speciesin Tauopathy Brains: An Extraction Protocol for Tau Oligomersand Aggregates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435Naruhiko Sahara and Taeko Kimura
27 Tau Assembly into Filaments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 447Mar Perez, Raquel Cuadros, and Miguel Medina
28 Quantitative Metabolomics in Alzheimer’s Disease: TechnicalConsiderations for Improved Reproducibility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463Sergio Veiga, Judith Wahrheit, Andres Rodrıguez-Martın,and Denise Sonntag
29 Detecting Circulating MicroRNAs as Biomarkers in Alzheimer’s Disease . . . . . . 471Aidan Kenny, Eva M. Jimenez-Mateos, Miguel Calero, Miguel Medina,and Tobias Engel
30 Luminescent-Conjugated Oligothiophene Probe Applicationsfor Fluorescence Imaging of Pure Amyloid Fibrils and ProteinAggregates in Tissues. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 485K. Peter R. Nilsson, Mikael Lindgren, and Per Hammarstrom
31 Characterization of Amyloid-β Plaques and AutofluorescentLipofuscin Aggregates in Alzheimer’s Disease Brain: A ConfocalMicroscopy Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 497Alejandra Kun, Fernando Gonzalez-Camacho, Silvia Hernandez,Alexandra Moreno-Garcıa, Olga Calero, and Miguel Calero
32 In Vivo Imaging of Tauopathy in Mice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 513Senthilkumar Krishnaswamy, Qian Wu, Yan Lin,Wajitha J. Rajamohamedsait, Hameetha B. Rajamohamedsait,and Einar M. Sigurdsson
33 In Vivo Evaluation of Neuronal Transport in Murine Modelsof Neurodegeneration Using Manganese-Enhanced MRI. . . . . . . . . . . . . . . . . . . . 527Anne Bertrand, Maria Baron, Dung M. Hoang, Lindsay K. Hill,Sebastian L. Mendoza, Einar M. Sigurdsson, and Youssef Z. Wadghiri
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 543
Contents ix
Contributors
FIROZ AKHTER � Department of Pharmacology and Toxicology, Higuchi Bioscience Center,School of Pharmacy, University of Kansas, Lawrence, KS, USA
LEIRE ALMANDOZ-GIL � Molecular Geriatrics, Department of Public Health and CaringSciences, Uppsala University, Uppsala, Sweden
OTTAVIO ARANCIO � Department of Pathology and Cell Biology, Columbia University,New York, NY, USA; The Taub Institute for Research on Alzheimer’s Disease and theAging Brain, Columbia University, New York, NY, USA; Department of Medicine,Columbia University, New York, NY, USA
ELENTINA K. ARGYROUSI � Department of Pathology and Cell Biology, Columbia University,New York, NY, USA; The Taub Institute for Research on Alzheimer’s Disease and theAging Brain, Columbia University, New York, NY, USA; Department of Psychiatry andNeuropsychology, School for Mental Health and Neuroscience (MHeNS), MaastrichtUniversity, Maastricht, The Netherlands
MARIA BARON � Department of Radiology, Center for Advanced Imaging Innovation andResearch (CAI2R), Bernard and Irene Schwartz Center for Biomedical Imaging,NYU School of Medicine and NYU Langone Health, New York, NY, USA
ILIA V. BASKAKOV � Department of Anatomy and Neurobiology, Center for BiomedicalEngineering and Technology, University of Maryland School of Medicine, Baltimore, MD,USA
JOAKIM BERGSTROM � Molecular Geriatrics, Department of Public Health and CaringSciences, Uppsala University, Uppsala, Sweden
ADELA BERNABEU-ZORNOZA � Unidad de Regeneraci�on Neural, Unidad Funcional deInvestigaci�on de Enfermedades Cr�onicas, Instituto de Salud Carlos III (ISCIII), Madrid,Spain
PAU BERNADO � Centre de Biochimie Structurale (CBS), INSERM, CNRS, Universite deMontpellier, Montpellier, France
ANNE BERTRAND � Department of Radiology, Center for Advanced Imaging Innovation andResearch (CAI2R), Bernard and Irene Schwartz Center for Biomedical Imaging, NYUSchool of Medicine and NYU Langone Health, New York, NY, USA; Institut du Cerveauet la Moelle (ICM), AP-HP—Hopital Pitie-Salpetriere, Boulevard de l’hopital, SorbonneUniversites, UPMC Univ. Paris 06, INSERM, CNRS, Paris, France; INRIA Paris,Aramis Project-Team, Paris, France
GAL BITAN � Department of Neurology, Molecular Biology Institute, Brain ResearchInstitute, David Geffen School of Medicine at UCLA, University of California, LosAngeles, Los Angeles, CA, USA
ERICA CABALLERO � Instituto de Biologıa y Genetica Molecular (IBGM), Universidad deValladolid y Consejo Superior de Investigaciones Cientıficas (CSIC), Valladolid, Spain
MIGUEL CALERO � Chronic Disease Programme-CROSADIS, CIBERNED, Queen SofiaFoundation Alzheimer Center, CIEN Foundation, Instituto de Salud Carlos III, Madrid,Spain
OLGA CALERO � Chronic Disease Programme-CROSADIS, Centro de Investigaci�onBiomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto deSalud Carlos III, Madrid, Spain
xi
MARIA CALVO-RODRIGUEZ � Instituto de Biologıa y Genetica Molecular (IBGM),Universidad de Valladolid y Consejo Superior de Investigaciones Cientıficas (CSIC),Valladolid, Spain; Alzheimer’s Disease Research Laboratory, Department of Neurology,Massachusetts General Institute for Neurodegenerative Disease, Massachusetts GeneralHospital, Harvard Medical School, Charlestown, MA, USA
NICCOLO CANDELISE � Department of Neurology, University Medicine Goettingen andGerman Center for Neurodegenerative Diseases (DZNE)–site Gottingen, Gottingen,Germany
MARIANA CARRETERO-MURILLO � George P. and Cynthia Woods Mitchell Center forNeurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX, USA;Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA;Department of Neuroscience and Cell Biology, University of Texas Medical Branch,Galveston, TX, USA
NATALIA CARULLA � Institute for Research in Biomedicine (IRB Barcelona), The BarcelonaInstitute Science and Technology, Barcelona, Spain; CBMN (UMR 5248), University ofBordeaux—CNRS—IPB, Institut Europeen de Chimie et Biologie, Pessac, France
MILAGROS CASTELLANOS � IMDEA Nacoscience, Madrid, SpainRAM REDDY CHANDUPATLA � German Center for Neurodegenerative Diseases (DZNE), Bonn,
Germany; Max-Planck-Institute for Metabolism Research (Cologne), Hamburg, GermanyMATTHEW R. CHAPMAN � Department of Molecular, Cellular, and Developmental Biology,
University of Michigan, Ann Arbor, MI, USASERENE W. CHEN � Department of Chemistry, University of Cambridge, Cambridge, UKSONIA CIUDAD � Institute for Research in Biomedicine (IRB Barcelona), The Barcelona
Institute Science and Technology, Barcelona, Spain; CBMN (UMR 5248), University ofBordeaux—CNRS—IPB, Institut Europeen de Chimie et Biologie, Pessac, France
JOSEPH L. CONOVALOFF � Department of Neurology, Molecular Biology Institute, BrainResearch Institute, David Geffen School of Medicine at UCLA, University of California,Los Angeles, Los Angeles, CA, USA
RAQUEL CORONEL � Unidad de Regeneraci�on Neural, Unidad Funcional de Investigaci�onde Enfermedades Cr�onicas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
NUNILO CREMADES � Institute for Biocomputation and Physics of Complex Systems (BIFI)-Joint Unit BIFI-IQFR (CSIC), University of Zaragoza, Zaragoza, Spain
JOANA S. CRISTOVAO � Biosystems and Integrative Sciences Institute, Faculdade de Ciencias,Universidade de Lisboa, Lisboa, Portugal; Departamento de Quımica e Bioquımica,Universidade de Lisboa, Lisboa, Portugal
RAQUEL CUADROS � Centro de Biologıa Molecular “Severo Ochoa” CSIC-UAM, Madrid,Spain
YAN DENG � Microscopy Core, New York University School of Medicine, New York, NY, USAHERMAN K. EDSKES � Laboratory of Biochemistry and Genetics, National Institute of Diabetes
Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USATOBIAS ENGEL � Department of Physiology and Medical Physics, Royal College of Surgeons in
Ireland, Dublin 2, IrelandMARGERY L. EVANS � Department of Molecular, Cellular, and Developmental Biology,
University of Michigan, Ann Arbor, MI, USAMARGARIDA GAIRI � NMR Facility, Scientific and Technological Centers, University of
Barcelona (CCiTUB), Barcelona, Spain
xii Contributors
MONICA GARCIA-DURILLO � Instituto de Biologıa y Genetica Molecular (IBGM),Universidad de Valladolid y Consejo Superior de Investigaciones Cientıficas (CSIC),Valladolid, Spain
MARIA GASSET � Institute of Physical Chemistry “Rocasolano”, Spanish National ResearchCouncil (CSIC), Madrid, Spain
FATIMA GASSET-ROSA � Department of Cellular and Molecular Biology, Centro deInvestigaciones Biol�ogicas (CSIC), Madrid, Spain; Department of Neurosciences, LudwigInstitute for Cancer Research, University of California in San Diego, La Jolla, CA, USA
JORGE GHISO � Department of Pathology, New York University School of Medicine, New York,NY, USA; Department of Psychiatry, New York University School of Medicine, New York,NY, USA
ELIZABETH GICHANA � Department of Molecular, Cellular, and Developmental Biology,University of Michigan, Ann Arbor, MI, USA
RAFAEL GIRALDO � Department of Cellular and Molecular Biology, Centro de InvestigacionesBiol�ogicas (CSIC), Madrid, Spain
CLAUDIO M. GOMES � Biosystems and Integrative Sciences Institute, Faculdade de Ciencias,Universidade de Lisboa, Lisboa, Portugal; Departamento de Quımica e Bioquımica,Universidade de Lisboa, Lisboa, Portugal
FERNANDO GONZALEZ-CAMACHO � Confocal Microscopy Unit, National Microbiology Centre,Instituto de Salud Carlos III, Madrid, Spain
PER HAMMARSTROM � IFM-Department of Chemistry, Linkoping University, Linkoping,Sweden
ERIC Y. HAYDEN � Department of Neurology, Molecular Biology Institute, Brain ResearchInstitute, David Geffen School of Medicine at UCLA, University of California, LosAngeles, Los Angeles, CA, USA
SILVIA HERNANDEZ � Confocal Microscopy Unit, National Microbiology Centre, Instituto deSalud Carlos III, Madrid, Spain
FATIMA HERRANZ-TRILLO � Department of Drug Design and Pharmacology, University ofCopenhagen, Copenhagen, Denmark; Centre de Biochimie Structurale (CBS), INSERM,CNRS, Universite de Montpellier, Montpellier, France
LINDSAY K. HILL � Department of Radiology, Center for Advanced Imaging Innovation andResearch (CAI2R), Bernard and Irene Schwartz Center for Biomedical Imaging, NYUSchool of Medicine and NYU Langone Health, New York, NY, USA; BiomedicalEngineering, SUNY Downstate Medical Center, Brooklyn, New York, NY, USA
DUNG M. HOANG � Department of Radiology, Center for Advanced Imaging Innovationand Research (CAI2R), Bernard and Irene Schwartz Center for Biomedical Imaging,NYU School of Medicine and NYU Langone Health, New York, NY, USA
ISTVAN HORVATH � Department of Biology and Biological Engineering, Chalmers Universityof Technology, Gothenburg, Sweden
ELISABET IHSE � Department of Immunology, Genetics and Pathology, Uppsala University,Uppsala, Sweden
MARTIN INGELSSON � Molecular Geriatrics, Department of Public Health and CaringSciences, Uppsala University, Uppsala, Sweden
EVA M. JIMENEZ-MATEOS � Department of Physiology and Medical Physics, Royal College ofSurgeons in Ireland, Dublin 2, Ireland
SENTHILVELRAJAN KANIYAPPAN � German Center for Neurodegenerative Diseases (DZNE),Bonn, Germany; Max-Planck-Institute for Metabolism Research (Cologne), Hamburg,Germany
Contributors xiii
ELIZAVETA KATORCHA � Department of Anatomy and Neurobiology, Center for BiomedicalEngineering and Technology, University of Maryland School of Medicine, Baltimore, MD,USA
RAKEZ KAYED � George P. and Cynthia Woods Mitchell Center for NeurodegenerativeDiseases, University of Texas Medical Branch, Galveston, TX, USA; Department ofNeurology, University of Texas Medical Branch, Galveston, TX, USA; Department ofNeuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX, USA
AIDAN KENNY � Department of Physiology and Medical Physics, Royal College of Surgeons inIreland, Dublin 2, Ireland
TAEKO KIMURA � Department of Functional Brain Imaging Research, National Institute ofRadiological Sciences, National Institutes for Quantum and Radiological Science andTechnology, Chiba, Japan
TUOMAS P. J. KNOWLES � Department of Chemistry, University of Cambridge, Cambridge,UK; Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge,UK
SENTHILKUMAR KRISHNASWAMY � Department of Neuroscience and Physiology, New YorkUniversity School of Medicine, New York, NY, USA
DMITRY KRYNDUSHKIN � Laboratory of Biochemistry and Genetics, National Institute ofDiabetes Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD,USA; Department of Pharmacology, Uniformed Services University of the Health Sciences,Bethesda, MD, USA
ALEJANDRA KUN � Biochemistry Section, Proteins and Nucleic Acids Department, Institutode Investigaciones Biol�ogicas Clemente Estable, Science School, Universidad de laRepublica, Montevideo, Uruguay
MARIA LACHGAR � Unidad de Regeneraci�on Neural, Unidad Funcional de Investigaci�onde Enfermedades Cr�onicas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
ANNETTE EVA LANGKILDE � Department of Drug Design and Pharmacology, University ofCopenhagen, Copenhagen, Denmark
YAN LIN � Department of Neuroscience and Physiology, New York University School ofMedicine, New York, NY, USA
MIKAEL LINDGREN � IFM-Department of Chemistry, Linkoping University, Linkoping,Sweden; Department of Physics, The Norwegian University of Science and Technology,Trondheim, Norway
SARA LINSE � Department of Biochemistry and Structural Biology, Lund University, Lund,Sweden
ISABEL LISTE � Unidad de Regeneraci�on Neural, Unidad Funcional de Investigaci�on deEnfermedades Cr�onicas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
FRANC LLORENS � Center for Networked Biomedical Research on NeurodegenerativeDiseases (CIBERNED), Barcelona, Spain
ECKHARD MANDELKOW � German Center for Neurodegenerative Diseases (DZNE), Bonn,Germany; Max-Planck-Institute for Metabolism Research (Cologne), Hamburg, Germany;Caesar Research Center, Bonn, Germany
JAVIER MARTINEZ � Institute of Physical Chemistry “Rocasolano”, Spanish National ResearchCouncil (CSIC), Madrid, Spain; Biosystems and Integrative Sciences Institute, Faculdade
xiv Contributors
de Ciencias, Universidade de Lisboa, Lisboa, Portugal; Departamento de Quımicae Bioquımica, Universidade de Lisboa, Lisboa, Portugal
ASHLEY MASON � Department of Neurology, Molecular Biology Institute, Brain ResearchInstitute, David Geffen School of Medicine at UCLA, University of California, LosAngeles, Los Angeles, CA, USA
RYAN MCGLINCHEY � Laboratory of Biochemistry and Genetics, National Institute ofDiabetes Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
MIGUEL MEDINA � CIBERNED, Queen Sofia Foundation Alzheimer Center, CIENFoundation, Instituto de Salud Carlos III, Madrid, Spain
GEORG MEISL � Department of Chemistry, University of Cambridge, Cambridge, UKSEBASTIAN L. MENDOZA � Department of Radiology, Center for Advanced Imaging
Innovation and Research (CAI2R), Bernard and Irene Schwartz Center for BiomedicalImaging, NYU School of Medicine and NYU Langone Health, New York, NY, USA
THOMAS C. T. MICHAELS � Department of Chemistry, University of Cambridge, Cambridge,UK; Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge,MA, USA
LAURA MOLINA-GARCIA � Department of Cellular and Molecular Biology, Centro deInvestigaciones Biol�ogicas (CSIC), Madrid, Spain; Department of Cell and DevelopmentalBiology, University College London, London, UK
LAURA MONTOYA � Institute of Physical Chemistry “Rocasolano”, Spanish National ResearchCouncil (CSIC), Madrid, Spain
MARIA MORENO-DEL ALAMO � Department of Cellular and Molecular Biology, Centro deInvestigaciones Biol�ogicas (CSIC), Madrid, Spain; Department of Microbial Biotechnology,National Centre for Biotechnology (CSIC), Madrid, Spain
SUSANA MORENO-DIAZ DE LA ESPINA � Department of Cellular and Molecular Biology,Centro de Investigaciones Biol�ogicas (CSIC), Madrid, Spain
ALEXANDRA MORENO-GARCIA � Chronic Disease Programme-CROSADIS, Instituto de SaludCarlos III, Madrid, Spain
THOMAS A. NEUBERT � Department of Biochemistry and Molecular Pharmacology, New YorkUniversity School of Medicine, New York, NY, USA; Kimmel Center for Biology andMedicine at the Skirball Institute, New York University School of Medicine, New York, NY,USA
RUSSELL E. NICHOLLS � Department of Pathology and Cell Biology, Columbia University,New York, NY, USA; The Taub Institute for Research on Alzheimer’s Disease and theAging Brain, Columbia University, New York, NY, USA
K. PETER R. NILSSON � IFM-Department of Chemistry, Linkoping University, Linkoping,Sweden
MARTI NINOT-PEDROSA � Institute for Research in Biomedicine (IRB Barcelona), TheBarcelona Institute Science and Technology, Barcelona, Spain; CBMN (UMR 5248),University of Bordeaux—CNRS—IPB, Institut Europeen de Chimie et Biologie, Pessac,France
LUCIA NUNEZ � Departmento de Bioquımica y Biologıa Molecular y Fisiologıa, Universidadde Valladolid, Valladolid, Spain; Instituto de Biologıa y Genetica Molecular (IBGM),Universidad de Valladolid y Consejo Superior de Investigaciones Cientıficas (CSIC),Valladolid, Spain
SOFIE NYSTROM � Chemistry, IFM-Department of Physics, Chemistry and Biology, LinkopingUniversity, Linkoping, Sweden
INGVAR H. OLAFSSON � Landspitali—The National University Hospital, Reykjavik, Iceland
Contributors xv
CHARLOTTE PALMER � Unidad de Regeneraci�on Neural, Unidad Funcional de Investigaci�onde Enfermedades Cr�onicas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
MAR PEREZ � Department of Anatomy, Histology and Neurosciences, Universidad Aut�onomade Madrid, Madrid, Spain
EDUARD PUIG � Institute for Research in Biomedicine (IRB Barcelona), The BarcelonaInstitute Science and Technology, Barcelona, Spain; CBMN (UMR 5248), University ofBordeaux—CNRS—IPB, Institut Europeen de Chimie et Biologie, Pessac, France
HAMEETHA B. RAJAMOHAMEDSAIT � Department of Neuroscience and Physiology, New YorkUniversity School of Medicine, New York, NY, USA
WAJITHA J. RAJAMOHAMEDSAIT � Department of Neuroscience and Physiology, New YorkUniversity School of Medicine, New York, NY, USA
SANDRA ROCHA � Department of Biology and Biological Engineering, Chalmers Universityof Technology, Gothenburg, Sweden
ANDRES RODRIGUEZ-MARTIN � Biocross S.L., Boecillo (Valladolid), SpainAGUEDA ROSTAGNO � Department of Pathology, New York University School of Medicine,
New York, NY, USANARUHIKO SAHARA � Department of Functional Brain Imaging Research, National Institute
of Radiological Sciences, National Institutes for Quantum and Radiological Science andTechnology, Chiba, Japan
ROSA SANCHEZ � Institute of Physical Chemistry “Rocasolano”, Spanish National ResearchCouncil (CSIC), Madrid, Spain
ALEXANDER SANDBERG � Chemistry, IFM-Department of Physics, Chemistry and Biology,Linkoping University, Linkoping, Sweden
MATTHIAS SCHMITZ � Department of Neurology, University Medicine Goettingen andGerman Center for Neurodegenerative Diseases (DZNE)–site Gottingen, Gottingen,Germany
URMI SENGUPTA � George P. and Cynthia Woods Mitchell Center for NeurodegenerativeDiseases, University of Texas Medical Branch, Galveston, TX, USA; Department ofNeurology, University of Texas Medical Branch, Galveston, TX, USA; Department ofNeuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX, USA
MONTSERRAT SERRA-BATISTE � Institute for Research in Biomedicine (IRB Barcelona),The Barcelona Institute Science and Technology, Barcelona, Spain
DOV B. SHAMIR � Department of Neuroscience and Physiology, New York University Schoolof Medicine, New York, NY, USA
FRANK SHEWMAKER � Department of Pharmacology, Uniformed Services University of theHealth Sciences, Bethesda, MD, USA
EINAR M. SIGURDSSON � Department of Neuroscience and Physiology, NYU School ofMedicine and NYU Langone Health, New York, NY, USA; Department of Psychiatry,NYU School of Medicine and NYU Langone Health, New York, NY, USA
DENISE SONNTAG � BIOCRATES Life Sciences AG, Innsbruck, AustriaALEXANDER A. SOSUNOV � College of Physicians and Surgeon of Columbia University,
New York, NY, USAAGNIESZKA STANISZEWSKI � Department of Pathology and Cell Biology, Columbia University,
New York, NY, USA; The Taub Institute for Research on Alzheimer’s Disease and theAging Brain, Columbia University, New York, NY, USA
DAVID B. TEPLOW � Department of Neurology, Molecular Biology Institute, Brain ResearchInstitute, David Geffen School of Medicine at UCLA, University of California, LosAngeles, Los Angeles, CA, USA
xvi Contributors
FINNBOGI R. THORMODSSON � Innovation Center Iceland, Reykjavik, IcelandSERGIO VEIGA � Biocross S.L., Valladolid, SpainBENTE VESTERGAARD � Department of Drug Design and Pharmacology, University of
Copenhagen, Copenhagen, DenmarkDADI TH. VILHJALMSSON � Skane University Hospital, Malmo, SwedenCARLOS VILLALOBOS � Instituto de Biologıa y Genetica Molecular (IBGM), Universidad de
Valladolid y Consejo Superior de Investigaciones Cientıficas (CSIC), Valladolid, SpainYOUSSEF Z. WADGHIRI � Department of Radiology, Center for Advanced Imaging
Innovation and Research (CAI2R), Bernard and Irene Schwartz Center for BiomedicalImaging, NYU School of Medicine and NYU Langone Health, New York, NY, USA
JUDITH WAHRHEIT � BIOCRATES Life Sciences AG, Innsbruck, AustriaGUNILLA T. WESTERMARK � Department of Medical Cell Biology, Uppsala University,
Uppsala, SwedenPERWESTERMARK � Department of Immunology, Genetics and Pathology, Uppsala University,
Uppsala, SwedenREED B. WICKNER � Laboratory of Biochemistry and Genetics, National Institute of Diabetes
Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USAPERNILLA WITTUNG-STAFSHEDE � Department of Biology and Biological Engineering,
Chalmers University of Technology, Gothenburg, SwedenQIAN WU � Department of Neuroscience and Physiology, New York University School of
Medicine, New York, NY, USASHI FANG YAN � Department of Pharmacology and Toxicology, Higuchi Bioscience Center,
School of Pharmacy, University of Kansas, Lawrence, KS, USASHIRLEY SHIDU YAN � Department of Pharmacology and Toxicology, Higuchi Bioscience
Center, School of Pharmacy, University of Kansas, Lawrence, KS, USAINGA ZERR � Department of Neurology, University Medicine Goettingen and German Center
for Neurodegenerative Diseases (DZNE)–site Gottingen, Gottingen, GermanyYIZHOU ZHOU � Department of Molecular, Cellular, and Developmental Biology, University
of Michigan, Ann Arbor, MI, USA
Contributors xvii