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

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Biomarkers for Alzheimer’s Disease Drug Development

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

Abstract

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).

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Acknowledgments

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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Authors and Affiliations

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

    Filippo Baldacci, Simone Lista & Harald Hampel

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

    Filippo Baldacci, Simone Lista & Harald Hampel

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

    Filippo Baldacci, Simone Lista & Harald Hampel

  4. 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

    Filippo Baldacci, Simone Lista & Harald Hampel

  5. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    Filippo Baldacci & Roberto Ceravolo

  6. Institute for Healthy Aging, University of North Texas Health Science Center, Fort Worth, TX, USA

    Sid E. O’Bryant

  7. Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, Rome, Italy

    Nicola Toschi

  8. Department of Radiology“Athinoula A. Martinos”, Center for Biomedical Imaging, Boston, MA, USA

    Nicola Toschi

  9. Harvard Medical School, Boston, MA, USA

    Nicola Toschi

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  1. Filippo Baldacci
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for the Alzheimer Precision Medicine Initiative (APMI)

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Correspondence to Simone Lista .

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

    Robert Perneczky

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Baldacci, F. et al. (2018). Blood-Based Biomarker Screening with Agnostic Biological Definitions for an Accurate Diagnosis Within the Dimensional Spectrum of Neurodegenerative Diseases. 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_9

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  • DOI: https://doi.org/10.1007/978-1-4939-7704-8_9

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