Blood-Based Biomarker Screening with Agnostic Biological Definitions for an Accurate Diagnosis Within the Dimensional Spectrum of Neurodegenerative Diseases

  • Filippo Baldacci
  • Simone ListaEmail author
  • Sid E. O’Bryant
  • Roberto Ceravolo
  • Nicola Toschi
  • Harald Hampel
  • for the Alzheimer Precision Medicine Initiative (APMI)
Part of the Methods in Molecular Biology book series (MIMB, volume 1750)


The discovery, development, and validation of novel candidate biomarkers in Alzheimer’s disease (AD) and other neurodegenerative diseases (NDs) are increasingly gaining momentum. As a result, evolving diagnostic research criteria of NDs are beginning to integrate biofluid and neuroimaging indicators of pathophysiological mechanisms. More than 10% of people aged over 65 suffer from NDs. There is an urgent need for a refined two-stage diagnostic model to first initiate an early, sensitive, and noninvasive process in primary care settings. Individuals that meet detection criteria will then be channeled to more specific, costly (positron-emission tomography), and invasive (cerebrospinal fluid) assessment methods for confirmatory biological characterization and diagnosis.

A reliable and sensitive blood test for AD and other NDs is not yet established; however, it would provide the golden screening gate for an efficient primary care management. A limitation to the development of a large-scale blood-screening biomarker-based test is the traditional application of clinically descriptive criteria for the categorization of single late-stage ND constructs. These are genetically and biologically heterogeneous, reflected in multiple pathophysiological mechanisms and subsequent pathologies throughout a dimensional continuum. Evidence suggests that a shared, “open-source” integrated multilevel categorization of NDs that clusters individuals based on descriptive clinical phenotypes and pathophysiological biomarker signatures will provide the next incremental step toward an improved diagnostic process of NDs. This intermediate objective toward unbiased biomarker-guided early detection of individuals at risk for NDs is currently carried out by the international pilot Alzheimer Precision Medicine Initiative Cohort Program (APMI-CP).

Key words

Neurodegenerative diseases Alzheimer’s disease Biomarkers Pathophysiology Alzheimer precision medicine initiative Systems biology Systems neurophysiology Precision medicine Blood Screening 



S.E.O. is supported by the National Institute on Aging of the National Institutes of Health under Award Numbers R01AG051848 and R56AG054073. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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. 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).

Disclosure Statement

S.L. received lecture honoraria from Roche. H.H. reports no conflict of interest with the content of the present manuscript. He serves as Senior Associate Editor for the Journal Alzheimer’s & Dementia; he has been a scientific consultant and/or speaker and/or attended scientific advisory boards of Axovant, Anavex, Eli Lilly and company, GE Healthcare, Cytox Ltd., Jung Diagnostics GmbH, Roche, Biogen Idec, Takeda-Zinfandel, Oryzon Genomics, and Qynapse; and he receives research support from the Association for Alzheimer Research (Paris), Pierre and Marie Curie University (Paris), and Pfizer & Avid (paid to institution); and he has patents, but receives no royalties. F.B., S.E.O., R.C., and N.T. declare no conflicts of interest.


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Copyright information

© Springer Science+Business Media, LLC 2018

Authors and Affiliations

  • Filippo Baldacci
    • 1
    • 2
    • 3
    • 4
    • 5
  • Simone Lista
    • 1
    • 2
    • 3
    • 4
    Email author
  • Sid E. O’Bryant
    • 6
  • Roberto Ceravolo
    • 5
  • Nicola Toschi
    • 7
    • 8
    • 9
  • Harald Hampel
    • 1
    • 2
    • 3
    • 4
  • for the Alzheimer Precision Medicine Initiative (APMI)
  1. 1.AXA Research Fund & UPMC ChairParisFrance
  2. 2.Sorbonne Université, AP-HP, GRC n° 21, Alzheimer Precision Medicine (APM)Hôpital de la Pitié-Salpêtrière, Boulevard de l’hôpitalParisFrance
  3. 3.Institut du Cerveau et de la Moelle Épinière (ICM), INSERM U 1127, CNRS UMR 7225Boulevard de l’hôpitalParisFrance
  4. 4.Institut de la Mémoire et de la Maladie d’Alzheimer (IM2A), Département de NeurologieHôpital de la Pitié-Salpêtrière, AP-HP, Boulevard de l’hôpitalParisFrance
  5. 5.Department of Clinical and Experimental MedicineUniversity of PisaPisaItaly
  6. 6.Institute for Healthy AgingUniversity of North Texas Health Science CenterFort WorthUSA
  7. 7.Department of Biomedicine and PreventionUniversity of Rome “Tor Vergata”RomeItaly
  8. 8.Department of Radiology“Athinoula A. Martinos”Center for Biomedical ImagingBostonUSA
  9. 9.Harvard Medical SchoolBostonUSA

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