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Systems Biology Methods for Alzheimer’s Disease Research Toward Molecular Signatures, Subtypes, and Stages and Precision Medicine: Application in Cohort Studies and Trials

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Biomarkers for Alzheimer’s Disease Drug Development

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1750))

Abstract

Alzheimer’s disease (AD) is a complex multifactorial disease, involving a combination of genomic, interactome, and environmental factors, with essential participation of (a) intrinsic genomic susceptibility and (b) a constant dynamic interplay between impaired pathways and central homeostatic networks of nerve cells. The proper investigation of the complexity of AD requires new holistic systems-level approaches, at both the experimental and computational level. Systems biology methods offer the potential to unveil new fundamental insights, basic mechanisms, and networks and their interplay. These may lead to the characterization of mechanism-based molecular signatures, and AD hallmarks at the earliest molecular and cellular levels (and beyond), for characterization of AD subtypes and stages, toward targeted interventions according to the evolving precision medicine paradigm. In this work, an update on advanced systems biology methods and strategies for holistic studies of multifactorial diseases—particularly AD—is presented. This includes next-generation genomics, neuroimaging and multi-omics methods, experimental and computational approaches, relevant disease models, and latest genome editing and single-cell technologies. Their progressive incorporation into basic research, cohort studies, and trials is beginning to provide novel insights into AD essential mechanisms, molecular signatures, and markers toward mechanism-based classification and staging, and tailored interventions. Selected methods which can be applied in cohort studies and trials, with the European Prevention of Alzheimer’s Dementia (EPAD) project as a reference example, are presented and discussed.

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Acknowledgments

This work was supported by Genetadi Biotech SL (Bizkaia, Spain). J.I.C. is the beneficiary of a senior prossgram (mode A) of Bizkaia:Xede Foundation. H.H. is supported by the AXA Research Fund, the Fondation Université Pierre et Marie Curie, and the Fondation pour la Recherche sur Alzheimer, Paris, France. Ce travail a bénéficié d’une aide de l’Etat “Investissements d’avenir” ANR-10-IAIHU-06 (H.H.). The research leading to these results has received funding from the program “Investissements d’avenir” ANR-10-IAIHU-06 (Agence Nationale de la Recherche-10-IA Agence Institut Hospitalo-Universitaire-6) (H.H.).

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Authors and Affiliations

  1. Genetadi Biotech S.L. Parque Tecnológico de Bizkaia, Derio, Bizkaia, Spain

    Juan I. Castrillo

  2. AXA Research Fund & UPMC Chair, F-75013, Paris, France

    Simone Lista & Harald Hampel

  3. Sorbonne Université, AP-HP, GRC n° 21, Alzheimer Precision Medicine (APM), Hôpital de la Pitié-Salpêtrière, Boulevard de l’hôpital, F-75013, Paris, France

    Simone Lista & Harald Hampel

  4. Institut du Cerveau et de la Moelle Épinière (ICM), INSERM U 1127, CNRS UMR 7225, Boulevard de l’hôpital, F-75013, Paris, France

    Simone Lista & Harald Hampel

  5. Institut de la Mémoire et de la Maladie d’Alzheimer (IM2A), Département de Neurologie, Hôpital de la Pitié-Salpêtrière, AP-HP, Boulevard de l’hôpital, F-75013, Paris, France

    Simone Lista & Harald Hampel

  6. Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK

    Craig W. Ritchie

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  1. Juan I. Castrillo
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  2. Simone Lista
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  3. Harald Hampel
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  4. Craig W. Ritchie
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Editors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität München, Munich, Germany

    Robert Perneczky

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Castrillo, J.I., Lista, S., Hampel, H., Ritchie, C.W. (2018). Systems Biology Methods for Alzheimer’s Disease Research Toward Molecular Signatures, Subtypes, and Stages and Precision Medicine: Application in Cohort Studies and Trials. In: Perneczky, R. (eds) Biomarkers for Alzheimer’s Disease Drug Development. Methods in Molecular Biology, vol 1750. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7704-8_3

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  • DOI: https://doi.org/10.1007/978-1-4939-7704-8_3

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