Neurodegenerative diseases : unifying principles

361 Pages·2017·12.598 MB·English

by  Cummings, Jeffrey L., Pillai, Jagan

NEURODEGENERATIVE DISEASES

NEURODEGENERATIVE
DISEASES
Unifying Principles
EDITED BY
JEFFREY L. CUMMINGS, MD, ScD
Director
Cleveland Clinic
Lou Ruvo Center for Brain Health
Las Vegas, NV
JAGAN A. PILLAI, MBBS, PhD
Cleveland Clinic
Lou Ruvo Center for Brain Health
Cleveland, OH
1
1
Oxford University Press is a department of the University of Oxford. It furthers
the University’s objective of excellence in research, scholarship, and education
by publishing worldwide. Oxford is a registered trade mark of Oxford University
Press in the UK and certain other countries.
Published in the United States of America by Oxford University Press
198 Madison Avenue, New York, NY 10016, United States of America.
© Oxford University Press 2017
All rights reserved. No part of this publication may be reproduced, stored in
a retrieval system, or transmitted, in any form or by any means, without the
prior permission in writing of Oxford University Press, or as expressly permitted
by law, by license, or under terms agreed with the appropriate reproduction
rights organization. Inquiries concerning reproduction outside the scope of the
above should be sent to the Rights Department, Oxford University Press, at the
address above.
You must not circulate this work in any other form
and you must impose this same condition on any acquirer.
Library of Congress Cataloging- in- Publication Data
Names: Cummings, Jeffrey L., 1948– , editor. | Pillai, Jagan, editor.
Title: Neurodegenerative diseases : unifying principles / edited by
Jeffrey L. Cummings, Jagan Pillai.
Other titles: Neurodegenerative diseases (Cummings)
Description: Oxford ; New York : Oxford University Press, [2017] | Includes
bibliographical references.
Identifiers: LCCN 2015038313 | ISBN 9780190233563 (alk. paper)
Subjects: | MESH: Neurodegenerative Diseases.
Classification: LCC RC522 | NLM WL 358.5 | DDC 616.8/ 3— dc23
LC record available at https://l ccn.loc.gov/ 2015038313
This material is not intended to be, and should not be considered, a substitute for medical or other professional advice.
Treatment for the conditions described in this material is highly dependent on the individual circumstances. And, while
this material is designed to offer accurate information with respect to the subject matter covered and to be current as of the
time it was written, research and knowledge about medical and health issues are constantly evolving and dose schedules
for medications are being revised continually, with new side effects recognized and accounted for regularly. Readers must
therefore always check the product information and clinical procedures with the most up-to-date published product
information and data sheets provided by the manufacturers and the most recent codes of conduct and safety regulation.
The publisher and the authors make no representations or warranties to readers, express or implied, as to the accuracy
or completeness of this material. Without limiting the foregoing, the publisher and the authors make no representations
or warranties as to the accuracy or efficacy of the drug dosages mentioned in the material. The authors and the publisher
do not accept, and expressly disclaim, any responsibility for any liability, loss or risk that may be claimed or incurred as a
consequence of the use and/or application of any of the contents of this material.
9 8 7 6 5 4 3 2 1
Printed by Sheridan Books, Inc., United States of America
To my parents who woke me up
JLC – J Lee and Ellen Cummings
JP – Veera and Ayyappan Pillai
To my mentors who showed me the way
JLC – Frank Benson and Larry Ruvo
JP – Jon Siegel, Christoph Schreiner, Joe Verghese, Doug Galasko
and Jeff Cummings
To my family who continue to make this journey meaningful
JC – Wife Kate and Daughter Juliana
JP – Wife Marianne and Daughter Veera
The Editors acknowledge Rhonda Heimer for her editorial assistance in
assembling the book and Karthik Sreenivasan for his draft of the book cover.

CONTENTS
Contributors  ix 9. Predementia Disorders:
Neurodegenerative Disorder
Predecessor States as Unifying
1. Neurodegenerative Diseases: Evolving
Clinical Features  134
Unifying Principles  1
Jagan A. Pillai
Jeffrey L. Cummings and Jagan A. Pillai
10. Genetics of Neurodegenerative
2. Neurodegenerative Diseases as Protein
Diseases: Sporadic and
Misfolding Disorders  15
Autosomal Dominant Forms  149
Tomohiro Nakamura
Lynn M. Bekris and James B. Leverenz
and Stuart A. Lipton
11. An Epigenetics Perspective
3. Calcium Hypothesis
on Diseases of the Central
of Neurodegeneration: The
Nervous System  185
Case of Alzheimer’s Disease and
Huntington’s Disease  27 Diego F. Mastroeni
Daniel A. Ryskamp, Elena Popugaeva, 12. Mitochondrial Changes
and Ilya Bezprozvanny and Bioenergetics in
Neurodegenerative Diseases  215
4. Neuroinflammation and
Neurodegenerative Diseases  40 Andrew B. Knott and
Ella Bossy- Wetzel
Taylor R. Jay, Shane M. Bemiller,
Lee E. Neilson, Paul J. Cheng-Hathaway, 13. Cell Culture, iPS Cells and
and Bruce T. Lamb Neurodegenerative Diseases  230
5. Prion Paradigm of Human Roxana Nat and Andreas Eigentler
Neurodegenerative Diseases Caused
14. Animal Models of Neurodegenerative
by Protein Misfolding  77
Diseases  242
Jiri G. Safar
David Baglietto- Vargas,
6. Neuropsychiatric Features Across Rahasson R. Ager, Rodrigo Medeiros,
Neurodegenerative Diseases  85 and Frank M. LaFerla
Claudia R. Padilla 15. Metal- Protein Attenuating
and Mario F. Mendez Compounds in Neurodegenerative
Diseases  263
7. Brain Circuits: Neurodegenerative
Diseases  98 Peng Lei, Scott Ayton,
and Ashley I. Bush
Juan Zhou and William W. Seeley
16. Disease- Modifying Therapies in
8. Fluid Biomarkers Indicative
Neurodegenerative Disorders  292
of Neurodegenerative Diseases  123
Janelle Drouin- Ouellet
Henrik Zetterberg
and Roger A. Barker
and Jonathan M. Schott
viii Contents
17. Immunotherapy 19. Conclusions on Neurodegenerative
for Neurodegenerative Disorders  307 Disorders: Unifying Principles  337
David Morgan Jagan A. Pillai
and Jeffrey L. Cummings
18. Clinical Trials and Drug
Development in Neurodegenerative
Diseases: Unifying Principles  323 Index  339
Jeffrey L. Cummings and Kate Zhong
CONTRIBUTORS
Rahasson R. Ager, PhD Ilya Bezprozvanny, PhD, DSci
Institute for Memory Impairments Department of Physiology
and Neurological Disorders UT Southwestern Medical Center
University of California Dallas, TX
Irvine, CA Laboratory of Molecular Neurodegeneration
St. Petersburg State Polytechnical University
Scott Ayton, PhD St. Petersburg, Russia
Oxidation Biology Unit
Florey Institute of Neuroscience and Ella Bossy- Wetzel, PhD
Mental Health Burnett School of Biomedical Sciences
The University of Melbourne College of Medicine
Parkville, Australia University of Central Florida
Orlando, FL
David Baglietto- Vargas, PhD
Department of Neurobiology Ashley I. Bush, MD, PhD
and Behavior Oxidation Biology Unit
Institute for Memory Impairments Florey Institute of Neuroscience and Mental Health
and Neurological Disorders The University of Melbourne
University of California Parkville, Australia
Irvine, CA
Paul J. Cheng- Hathaway, BA
Roger A. Barker, PhD Department of Neurosciences
John van Geest Centre for Brain Repair Case Western Reserve University
Department of Clinical Neuroscience Cleveland, OH
University of Cambridge
Cambridge, UK Jeffrey L. Cummings, MD, ScD
Director
Lynn M. Bekris, PhD Lou Ruvo Center for Brain Health
Cleveland Clinic Neurological Institute
Lerner Research Institute Cleveland Clinic
Genomic Medicine Institute Las Vegas, NV
Cleveland, OH
Janelle Drouin- Ouellet, PhD
Shane M. Bemiller, PhD Wallenberg Neuroscience Center and
Stark Neurosciences Research Institute Lund Stem Cell Center
Indiana University School Department of Experimental Medical Science
of Medicine Lund University
Indianapolis, IN Lund, Sweden