Systems Biology of Alzheimer's Disease

581 Pages·2015·14.29 MB·English

by  Juan I. Castrillo

Methods in
Molecular Biology 1303
Juan I. Castrillo
Stephen G. Oliver Editors
Systems Biology
of Alzheimer’s
Disease
M M B
ETHODS IN OLECULAR IOLOGY
Series Editor
John M. Walker
School of Life and Medical Sciences
University of Hertfordshire
Hat fi eld, Hertfordshire, AL10 9AB, UK
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Systems Biology
of Alzheimer’s Disease
Edited by
Juan I. Castrillo
Department of Biochemistry & Cambridge Systems Biology Centre, University of Cambridge, Cambridge, UK;
Genetadi Biotech S.L. Parque Tecnológico de Bizkaia, Derio, Bizkaia, Spain
Stephen G. Oliver
Department of Biochemistry & Cambridge Systems Biology Centre, University of Cambridge, Cambridge, UK
Editors
Juan I. Castrillo Stephen G . Oliver
Department of Biochemistry & Department of Biochemistry &
Cambridge Systems Biology Centre Cambridge Systems Biology Centre
University of Cambridge University of Cambridge
Cambridge, UK Cambridge, UK
Genetadi Biotech S.L. Parque
Tecnológico de Bizkaia
Derio, Bizkaia, Spain
ISSN 1064-3745 ISSN 1940-6029 (electronic)
Methods in Molecular Biology
ISBN 978-1-4939-2626-8 ISBN 978-1-4939-2627-5 (eBook)
DOI 10.1007/978-1-4939-2627-5
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Prefa ce
Alzheimer’s disease (AD), the most common form of dementia, currently affects over 44 mil-
lion individuals worldwide; its incidence is set to almost double by 2030 and more than triple
by 2050. The global cost of dementia was estimated in 2010 at USD 604 billion and is likely
to rise. Strong support exists toward progress on risk reduction via protective and modifi able
factors, early diagnosis, and timely intervention (Prince et al. 2011; WHO 2012; ADI 2014).
Alzheimer’s and many other neurodegenerative disorders are multifactorial in nature,
involving a combination of genomic, epigenomic, networks dynamic, and environmental
factors. The interplay of disease mechanisms and homeostatic biological networks will
underlie the time of onset and rate of progression of the disease, with a cascade of down-
stream effects resulting in a range of patient-specifi c phenotypes. The proper investigation
of the complexity of the disease requires new integrative Systems Biology approaches, at
both the experimental and computational level. The practical goals of such investigation
include improved classifi cation of risks and the characterization and detection of the fi rst
imbalances that underlie the onset of the disease, in the expectation that early diagnosis will
enable tailored and timely interventions.
This book addresses such an integrated approach to Alzheimer’s disease and comprises
six parts: In Part I (Chapters 1 and 2 ) , we present AD as a complex multifactorial disease,
with intrinsic susceptibility and network dynamics, for which integrative Systems Biology
experimental and computational approaches are necessary. In Part II (Chapters 3 – 10 ), an
up-to-date view of relevant pathways and networks underlying AD is provided. In P art III
(Chapters 11 – 16 ) , a number of the main disease models recapitulating AD features, with
latest studies and methods, are presented. In Part IV , “Experimental Systems Biology”
(Chapters 17 – 25 ), we present a perspective on next-generation molecular and high-
throughput methods for the study of AD susceptibility and the characterization of the
pathways and networks underlying the disease. These are applicable not only to AD but also
to other multifactorial diseases. In Part V , “Computational Systems Biology” (Chapters
26 – 30 ) , the latest computational and integrative network biology approaches are presented.
Finally, in Part VI , “AD in Practice. From Systems Biology to Systems Medicine” (Chapters
3 1 – 33 ) , selected examples of studies and strategies toward earlier diagnosis and tailored
therapeutic intervention are included.
This book is intended for postgraduate students, postdoctoral researchers, and experts
in different fi elds with an interest in comprehensive Systems Biology strategies applicable to
AD and other complex multifactorial diseases (including other neurodegenerative diseases
and cancers). We aim to present Systems Biology, including both experimental and compu-
tational approaches, as a new strategy for the study of AD and other dynamic multifactorial
diseases, 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 com-
plement other excellent volumes and monographs on AD that cover fundamental, physio-
logical, or medical aspects of the disease.
Cambridge, UK Juan I. Castrillo
Stephen G. Oliver
v
vi Preface
References
Prince M, Bryce R, Ferri C (2011) World Alzheimer ( h ttp://www.who.int/mental_health/publications/
Report 2011. The benefi ts of early diagnosis and dementia_report_2012/en/ )
intervention. Alzheimer’s disease International Alzheimer’s Disease International (2014) World
(ADI) 2011. ( h ttp://www.alz.co.uk/research/ Alzheimer Report 2014: dementia and risk
WorldAlzheimerReport2011.pdf ) reduction (an analysis of protective and modifi -
World Health Organization (2012) Dementia: a able factors) ( h ttp://www.alz.co.uk/research/
public health priority. World Health Organization world-report-2014 )
and Alzheimer’s Disease International, Geneva.
Contents
Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . x i
PART I SYSTEMS BIOLOGY OF MULTIFACTORIAL DISEASES:
ALZHEIMER’S DISEASE
1 Alzheimer’s as a Systems-Level Disease Involving the Interplay
of Multiple Cellular Networks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Juan I. Castrillo and S tephen G . Oliver
2 A pplication of Systems Theory in Longitudinal Studies on the Origin
and Progression of Alzheimer’s Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Simone Lista , Zaven S . K hachaturian , D an R ujescu , Francesco G araci ,
Bruno Dubois , and Harald H ampel
PART II A LZHEIMER’S DISEASE: MAIN UNDERLYING PATHWAYS
AND NETWORKS
3 The APP Proteolytic System and Its Interactions with Dynamic
Networks in Alzheimer’s Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
Sally Hunter , Steven M artin , and Carol B rayne
4 E ffects of Mild and Severe Oxidative Stress on BACE1 Expression
and APP Amyloidogenic Processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
Jiangli T an , Q iao-Xin Li , and Genevieve E vin
5 Advanced Assay Monitoring APP-Carboxyl-Terminal Fragments
as Markers of APP Processing in Alzheimer Disease Mouse Models. . . . . . . . . 117
Ana García-Osta and Mar C uadrado-Tejedor
6 O ptical Super-Resolution Imaging of β-Amyloid Aggregation
In Vitro and In Vivo: Method and Techniques . . . . . . . . . . . . . . . . . . . . . . . . 125
Dorothea P inotsi , Gabriele S . K aminski Schierle ,
and C lemens F . K aminski
7 Protocols for Monitoring the Development of Tau Pathology
in Alzheimer’s Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
Alberto Rábano , Raquel Cuadros , P aula Merino-Serráis ,
Izaskun Rodal , Ruth Benavides-Piccione , E lena G ómez ,
Miguel Medina , Javier DeFelipe , and Jesús Avila
8 L C3-II Tagging and Western Blotting for Monitoring Autophagic
Activity in Mammalian Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 61
Anne S treeter , Fiona M . M enzies , and D avid C. R ubinsztein
9 Advanced Mitochondrial Respiration Assay for Evaluation
of Mitochondrial Dysfunction in Alzheimer’s Disease . . . . . . . . . . . . . . . . . . . 1 71
Amandine Grimm , Karen S chmitt , and A nne Eckert
vii
viii Contents
10 Analysis of Microglial Proliferation in Alzheimer’s Disease. . . . . . . . . . . . . . . . 1 85
Diego Gomez-Nicola and V. H ugh Perry
PART III COMPREHENSIVE DISEASE MODELS RECAPITULATING
ALZHEIMER’S DISEASE FEATURES: FROM CELLULAR
MODELS TO HUMAN
11 Yeast as a Model for Alzheimer’s Disease: Latest Studies
and Advanced Strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 97
Mathias Verduyckt , H élène V ignaud , Tine Bynens ,
Jeff V an den Brande , Vanessa F ranssens , Christophe Cullin ,
and J oris Winderickx
12 Yeast as a Model for Studies on Aβ Aggregation Toxicity
in Alzheimer’s Disease, Autophagic Responses, and Drug Screening . . . . . . . . 217
Afsaneh P orzoor and I an Macreadie
13 D rosophila melanogaster as a Model for Studies on the Early Stages
of Alzheimer’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 27
Jung Yeon Lim , Stanislav O tt , and Damian C. C rowther
14 C hronic Mild Stress Assay Leading to Early Onset and Propagation
of Alzheimer’s Disease Phenotype in Mouse Models . . . . . . . . . . . . . . . . . . . . 2 41
Mar C uadrado-Tejedor and A na G arcía-Osta
15 Gene Expression Studies on Human Trisomy 21 iPSCs and Neurons:
Towards Mechanisms Underlying Down’s Syndrome and Early
Alzheimer’s Disease-Like Pathologies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 47
Jason P. Weick , H uining K ang , George F . B onadurer III ,
and A nita B hattacharyya
16 Cortical Differentiation of Human Pluripotent Cells
for In Vitro Modeling of Alzheimer’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . 2 67
Nathalie G. S aurat , Frederick J. L ivesey , and Steven M oore
PART IV EXPERIMENTAL SYSTEMS BIOLOGY: NEXT GENERATION
MOLECULAR AND HIGH-THROUGHPUT METHODS
FOR THE STUDY OF DISEASE SUSCEPTIBILITY AND NETWORKS
DYNAMICS INTERPLAY IN COMPLEX DISEASES
17 Next Generation Sequencing in Alzheimer’s Disease. . . . . . . . . . . . . . . . . . . . 2 81
Lars Bertram
18 Pooled-DNA Sequencing for Elucidating New Genomic Risk Factors,
Rare Variants Underlying Alzheimer’s Disease. . . . . . . . . . . . . . . . . . . . . . . . . 299
Sheng C hih Jin , B runo A . B enitez , Yuetiva Deming ,
and Carlos C ruchaga
19 N ew Genome-Wide Methods for Elucidation of Candidate Copy Number
Variations (CNVs) Contributing to Alzheimer’s Disease Heritability . . . . . . . . 3 15
Kinga S zigeti
20 R NA-Sequencing to Elucidate Early Patterns of Dysregulation
Underlying the Onset of Alzheimer’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . 3 27
Bei J un Chen , J ames D . Mills , C aroline J anitz , and Michael Janitz
Contents ix
21 Systems Biology Approaches to the Study of Biological Networks
Underlying Alzheimer’s Disease: Role of miRNAs. . . . . . . . . . . . . . . . . . . . . . 349
Wera R oth , D avid H ecker , and Eugenio F ava
22 The Emerging Role of Metalloproteomics in Alzheimer’s Disease Research. . . . . 3 79
Dominic J . Hare , A lan R embach , and Blaine R. R oberts
23 Redox Proteomics in Human Biofluids: Sample Preparation, Separation
and Immunochemical Tagging for Analysis of Protein Oxidation. . . . . . . . . . . 391
Fabio Di D omenico , M arzia P erluigi , and D . A llan B utterfield
24 Advanced Shotgun Lipidomics for Characterization of Altered Lipid Patterns
in Neurodegenerative Diseases and Brain Injury . . . . . . . . . . . . . . . . . . . . . . . 405
Miao Wang and Xianlin H an
25 AlzPathway, an Updated Map of Curated Signaling Pathways:
Towards Deciphering Alzheimer’s Disease Pathogenesis . . . . . . . . . . . . . . . . . 4 23
Soichi Ogishima , S atoshi M izuno , M asataka Kikuchi ,
Akinori Miyashita , Ryozo K uwano , H iroshi Tanaka , and Jun Nakaya
PART V COMPUTATIONAL SYSTEMS BIOLOGY, NETWORK BIOLOGY:
NEXT GENERATION COMPUTATIONAL AND INTEGRATIVE
NETWORK BIOLOGY APPROACHES FOR THE STUDY
OF MODULES, NETWORK DYNAMICS, AND THEIR INTERPLAY
IN COMPLEX DISEASES
26 A Computational Network Biology Approach to Uncover Novel
Genes Related to Alzheimer’s Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435
Andreas Z anzoni
27 Network Approaches to the Understanding of Alzheimer’s Disease:
From Model Organisms to Humans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 47
Justin Y erbury , Dan B ean , and Giorgio Favrin
28 Characterization of Genetic Networks Associated with Alzheimer’s Disease. . . . . 4 59
Bin Z hang , L inh Tran , Valur E milsson , and Jun Zhu
29 Network-Based Analysis for Uncovering Mechanisms Underlying
Alzheimer’s Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 79
Masataka K ikuchi , Soichi O gishima , S atoshi Mizuno ,
Akinori Miyashita , R yozo K uwano , Jun N akaya , and Hiroshi Tanaka
30 T he SDREM Method for Reconstructing Signaling and Regulatory
Response Networks: Applications for Studying Disease Progression. . . . . . . . . 493
Anthony G itter and Ziv B ar-Joseph
PART VI SYSTEMS BIOLOGY OF ALZHEIMER’S DISEASE IN PRACTICE:
FROM SYSTEMS BIOLOGY TO EARLY DIAGNOSTICS
AND SYSTEMS MEDICINE
31 Advanced Neuroimaging Methods Towards Characterization
of Early Stages of Alzheimer’s Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 509
Jorge Sepulcre and Joseph C . M asdeu