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

  • Juan I. Castrillo
  • Simone Lista
  • Harald Hampel
  • Craig W. Ritchie
Part of the Methods in Molecular Biology book series (MIMB, volume 1750)


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.

Key words

Alzheimer’s disease (AD) Systems biology Omics Interactomes Networks APP Amyloid-β (Aβ) Tau Proteinopathy Homeostasis networks Proteostasis Experimental systems biology Next-generation genomics Neuroimaging Next-generation omics techniques Computational systems biology Network biology Molecular biomarkers Standardization Validation Risk classification Staging AD subtypes AD stages Tailored treatments Clinical trials European Prevention of Alzheimer’s Dementia project EPAD Precision medicine 



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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Copyright information

© Springer Science+Business Media, LLC 2018

Authors and Affiliations

  • Juan I. Castrillo
    • 1
  • Simone Lista
    • 2
    • 3
    • 4
    • 5
  • Harald Hampel
    • 2
    • 3
    • 4
    • 5
  • Craig W. Ritchie
    • 6
  1. 1.Genetadi Biotech S.L. Parque Tecnológico de BizkaiaDerioSpain
  2. 2.AXA Research Fund & UPMC ChairParisFrance
  3. 3.Sorbonne Université, AP-HP, GRC n° 21, Alzheimer Precision Medicine (APM)Hôpital de la Pitié-Salpêtrière, Boulevard de l’hôpitalParisFrance
  4. 4.Institut du Cerveau et de la Moelle Épinière (ICM), INSERM U 1127, CNRS UMR 7225Boulevard de l’hôpitalParisFrance
  5. 5.Institut de la Mémoire et de la Maladie d’Alzheimer (IM2A), Département de NeurologieHôpital de la Pitié-Salpêtrière, AP-HP, Boulevard de l’hôpitalParisFrance
  6. 6.Centre for Clinical Brain SciencesUniversity of EdinburghEdinburghUK

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