Biomarkers for Preclinical Alzheimer’s Disease

271 Pages·2018·8.12 MB·English

by  Robert Perneczky (eds.)

Neuromethods 137
Robert Perneczky Editor
Biomarkers
for Preclinical
Alzheimer ’s
Disease
N
euromethods
Series Editor
Wolfgang Walz
University of Saskatchewan
Saskatoon, SK, Canada
For further volumes:
http://www.springer.com/series/7657
Biomarkers for Preclinical
Alzheimer’s Disease
Edited by
Robert Perneczky
Department of Psychiatry and Psychotherapy,
Ludwig-Maximilians-Universität München,
Munich, Germany
Editor
Robert Perneczky
Department of Psychiatry and Psychotherapy
Ludwig-Maximilians-Universität München
Munich, Germany
ISSN 0893-2336 ISSN 1940-6045 (electronic)
Neuromethods
ISBN 978-1-4939-7673-7 ISBN 978-1-4939-7674-4 (eBook)
https://doi.org/10.1007/978-1-4939-7674-4
Library of Congress Control Number: 2017964263
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Series Preface
Experimental life sciences have two basic foundations: concepts and tools. The Neuromethods
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Saskatoon, Canada Wolfgang Walz
v
Preface
The constantly increasing number of individuals with dementia due to Alzheimer’s disease
(AD) poses a significant financial and emotional burden on the affected families and the
global society. Therapeutic strategies designed to treat symptoms or alter the disease course
have so far failed to make a positive impact, despite billions of US dollars of R&D invest-
ments and massive efforts of the industry and academic communities. These failures in
treatment have led many to believe that symptomatic AD, including its earliest clinical
stages, is resistant to drug interventions.
The recently increased focus on biomarkers to diagnose early disease is fuelled by the
hope of identifying a therapeutic window, in which the brain is still largely intact and there-
fore amenable to treatment effects. The ability of biomarkers to adequately define the pre-
clinical (i.e., at risk of AD dementia) disease stage may ultimately allow novel or repurposed
drugs to finally achieve clinically meaningful results for the affected individuals and to help
to prevent dementia and associated disability.
This book discusses the usefulness of established biomarkers (imaging, fluid, and genetic)
to detect preclinical AD, providing detailed protocols for state-of-the-art biomarker mea-
surement and analysis. It is also explained how cutting-edge technology is used to develop
novel improved biomarkers for the earliest, presymptomatic stages of AD. Our book aims to
provide a comprehensive overview specifically of biomarkers for the earliest detectable dis-
ease stages. All previous publications cover biomarkers for clinical, symptomatic AD.
This publication comprises five parts: In Part I (Chaps. 1 and 2) we explain why AD is
one of the major challenges for the global societies and healthcare systems, which highlights
the urgent need for improved approaches for early diagnosis enabling disease prevention. In
Part II (Chaps. 3–5) clinical and research concepts are presented, which are important to
improve early recognition of AD. Part III (Chaps. 6–10) provides a comprehensive over-
view of methods currently used in the AD diagnostic work-up, and it is explained how these
methods can be applied to preclinical disease. In Part IV (Chaps. 11–15) cutting-edge tech-
nology innovations and their value for early AD diagnosis are discussed. Finally, in Part V
(Chaps. 16–18), we consider important ethical considerations in relation to biomarker-based
early diagnosis, and we also discuss the meaningfulness of biomarker endpoints in clinical
AD research.
The book is targeted at individuals with an interest in the use of advanced biomarker
strategies to significantly improve the early diagnosis of AD, and thereby to accelerate the
development of effective, disease-modifying drugs. This includes researchers, clinicians,
and those interested in regulatory and medical affairs, both from academia and industry. We
wish to present biomarker development approaches as a strategy for the study of AD with
the hope and expectation that the results will translate into more effective diagnosis and
treatment and improved public health policies. We expect this book to complement other
excellent volumes and monographs on AD that cover basic science or clinical aspects of the
disease.
London, UK Robert Perneczky
vii
Contents
Series Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
Part I alzheImer’s DIsease as a socIetal challenge
1 Worldwide Economic Costs and Societal Burden of Dementia................. 3
Junfang Xu and Chengxuan Qiu
2 Epidemiology and Risk Factors of Alzheimer’s Disease: A Focus on Diet......... 15
Cécilia Samieri
Part II DIagnostIc concePts
3 The Dimensional Structure of Subjective Cognitive Decline .................. 45
Miguel A. Fernández-Blázquez, Marina Ávila-Villanueva,
and Miguel Medina
4 Deriving and Testing the Validity of Cognitive Reserve Candidates............. 63
Yaakov Stern and Christian Habeck
5 Methods for Pathological Classification of Alzheimer’s Disease................ 71
Johannes Attems, Kirsty E. McAleese, and Lauren Walker
Part III establIsheD markers of PathoPhysIology anD rIsk
6 Cerebrospinal Fluid Biomarkers of Preclinical Alzheimer’s Disease ............. 93
Panagiotis Alexopoulos and Chaido Sirinian
7 Brain Structural Imaging in Alzheimer’s Disease........................... 107
Sven Haller, Davide Zanchi, Cristelle Rodriguez,
and Panteleimon Giannakopoulos
8 Brain Functional Imaging in Preclinical Alzheimer’s Disease . . . . . . . . . . . . . . . . . . 119
Peter Häussermann, Thorsten Bartsch, and Oliver Granert
9 Imaging of Brain Amyloid Load in Early Alzheimer’s Disease ................. 149
Timo Grimmer and Jennifer Grace Perryman
10 Functional EEG Connectivity Alterations in Alzheimer’s Disease............... 157
Florian Hatz and Peter Fuhr
Part IV bIomarker DIscoVery
11 A Selected Reaction Monitoring Protocol for the Measurement
of sTREM2 in Cerebrospinal Fluid..................................... 169
Amanda J. Heslegrave, Wendy E. Heywood, Kevin M. Mills,
and Henrik Zetterberg
ix
x Contents
12 Soluble Amyloid Precursor Proteins in Blood: Methods and Challenges ......... 179
Robert Perneczky and Panagiotis Alexopoulos
13 Tau Imaging in Preclinical Alzheimer’s Disease............................ 189
Paul Edison
14 Retinal Imaging in Early Alzheimer’s Disease ............................. 199
Tom MacGillivray, Sarah McGrory, Tom Pearson, and James Cameron
15 In Vivo Volumetry of the Cholinergic Basal Forebrain ...................... 213
Michel J. Grothe, Ingo Kilimann, Lea Grinberg, Helmut Heinsen,
and Stefan Teipel
Part V PatIent benefIt anD ethIcal consIDeratIons
16 Clinical Meaningfulness of Biomarker Endpoints in Alzheimer’s
Disease Research................................................... 235
Kok Pin Ng, Tharick A. Pascoal, Xiaofeng Li, Pedro Rosa-Neto,
and Serge Gauthier
17 The Ethics of Biomarker-Based Preclinical Diagnosis of Alzheimer’s Disease...... 249
Alexander F. Kurz and Nicola T. Lautenschlager
18 Shared Decision-Making and Important Medical and Social Decisions
in the Context of Early Diagnosis of Alzheimer’s Disease .................... 259
Katharina Bronner and Johannes Hamann
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271
Contributors
marIna ÁVIla-VIllanueVa • Alzheimer Disease Research Unit, CIEN Foundation, Carlos
III Institute of Health, Queen Sofía Foundation Alzheimer Center, Madrid, Spain
PanagIotIs alexoPoulos • Department of Psychiatry, University Hospital of Patras,
University of Patras, Patras, Greece; Department of Psychiatry and Psychotherapy,
Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
Johannes attems • Institute for Neuroscience, Newcastle University, Newcastle upon
Tyne, UK
thorsten bartsch • Department of Neurology, Memory Disorders and Plasticity Group,
Dementia and Alzheimer’s Clinic, University Hospital Schleswig-Holstein, Kiel,
Germany
katharIna bronner • Department of Psychiatry and Psychotherapy, Technische
Universität München, Munich, Germany
James cameron • Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh,
UK
Paul eDIson • Division of Brain Sciences, Department of Medicine, Neurology Imaging
Unit, Imperial College London, Hammersmith Hospital, London, UK; Department of
Psychological Medicine, Cardiff University School of Medicine, Cardiff, UK
mIguel a. fernÁnDez-blÁzquez • Alzheimer Disease Research Unit, CIEN Foundation,
Carlos III Institute of Health, Queen Sofía Foundation Alzheimer Center, Madrid, Spain
Peter fuhr • Section of Clinical Neurophysiology, Department of Neurology,
Hospital of the University of Basel, Basel, Switzerland
serge gauthIer • The McGill University Research Centre for Studies in Aging,
McGill University, Montreal, QC, Canada
PanteleImon gIannakoPoulos • Department of Psychiatry, Faculty of Medicine,
University of Geneva, Geneva, Switzerland; Division of Institutional Measures,
Medical Direction, University Hospitals of Geneva, Belle-Idée, Chêne-Bourg, Switzerland
olIVer granert • Department of Neurology, Memory Disorders and Plasticity Group,
Dementia and Alzheimer’s Clinic, University Hospital Schleswig-Holstein, Kiel,
Germany
tImo grImmer • Centre for Cognitive Disorders, Department of Psychiatry
and Psychotherapy, Klinikum rechts der Isar, Technical University of Munich, Munich,
Germany
lea grInberg • Department of Neurology, University of California, San Francisco, CA,
USA
mIchel J. grothe • German Center for Neurodegenerative Diseases (DZNE), Rostock,
Germany
chrIstIan habeck • Cognitive Neuroscience Division, Department of Neurology,
College of Physicians and Surgeons, Columbia University, New York, NY, USA
sVen haller • Affidea Carouge Radiologic Diagnostic Center, Geneva, Switzerland;
Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden;
Department of Neuroradiology, University Hospital Freiburg, Freiburg, Germany;
Department of Neuroradiology, Faculty of Medicine, University of Geneva, Geneva,
Switzerland
xi
xii Contributors
Johannes hamann • Department of Psychiatry and Psychotherapy, Technische Universität
München, Munich, Germany
florIan hatz • Section of Clinical Neurophysiology, Department of Neurology,
Hospital of the University of Basel, Basel, Switzerland
Peter häussermann • Department of Geriatric Psychiatry, LVR Klinik Köln, Academic
Teaching Hospital, University of Cologne, Köln, Germany
helmut heInsen • Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, Brazil;
Department of Psychiatry, Psychosomatics and Psychotherapy, Julius-Maximilians-
University, Würzburg, Germany
amanDa J. heslegraVe • Department of Molecular Neuroscience, UCL Institute
of Neurology, London, UK
WenDy e. heyWooD • Centre for Translational Omics, University College London
Institute of ChildHealth, London, UK
Ingo kIlImann • German Center for Neurodegenerative Diseases (DZNE), Rostock,
Germany; Department of Psychosomatic Medicine, University of Rostock, Rostock,
Germany
alexanDer f. kurz • Department of Psychiatry and Psychotherapy, Klinikum rechts der
Isar, Technische Universität München, Munich, Germany
nIcola t. lautenschlager • Academic Unit for Psychiatry of Old Age, Department
of Psychiatry, The University of Melbourne and NorthWestern Mental Health,
Mental Health, Melbourne, Australia
xIaofeng lI • The McGill University Research Centre for Studies in Aging,
McGill University, Montreal, QC, Canada; Department of Neurology,
The Second Affiliated Hospital of Chongqing Medical University, Chongqing,
People’s Republic of China
tom macgIllIVray • Centre for Clinical Brain Sciences, University of Edinburgh,
Edinburgh, UK
kIrsty e. mcaleese • Institute for Neuroscience, Newcastle University, Newcastle upon
Tyne, UK
sarah mcgrory • Centre for Cognitive Ageing and Cognitive Epidemiology,
University of Edinburgh, Edinburgh, UK
mIguel meDIna • Alzheimer Disease Research Unit, CIEN Foundation, Carlos III
Institute of Health, Queen Sofía Foundation Alzheimer Center, Madrid, Spain;
CIBERNED (Network Center for Biomedical Research in Neurodegenerative Diseases),
Universidad Autónoma de Madrid, Madrid, Spain
keVIn m. mIlls • Centre for Translational Omics, University College London Institute
of ChildHealth, London, UK
kok PIn ng • The McGill University Research Centre for Studies in Aging,
McGill University, Montreal, QC, Canada; Department of Neurology,
National Neuroscience Institute, Singapore, Singapore
tharIck a. Pascoal • The McGill University Research Centre for Studies in Aging,
McGill University, Montreal, QC, Canada
tom Pearson • Centre for Clinical Brain Sciences, University of Edinburgh,
Edinburgh, UK
robert Perneczky • Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-
Universität München, Munich, Germany
JennIfer grace Perryman • Ludwig-Maximilians-University Munich, Munich, Germany