Blood-based diagnostics of Alzheimer’s disease

ABSTRACT

Introduction: This review is focused on the methods used for biomarker discovery for Alzheimer’s disease (AD) in blood rather than on the nature of the biomarkers themselves.

Areas covered: All biomarker discovery programs explicitly rely on contrasts in phenotype as a basis for defining differences. In this review, we explore the basis of contrasting choices as a function of the type of biomarker (genetic, protein, metabolite, non-coding RNA, or pathogenic epitope). We also provide an overview of the capacity to identify pathogenic epitopes with our new platform called Aptamarkers. It is suggested that a pre-existing hypothesis regarding the pathophysiology of the disease can act as a constraint to the development of biomarkers.

Expert opinion: Limiting putative biomarkers to those that have a postulated role in the pathophysiology of disease imposes an unrealistic constraint on biomarker development. The understanding of Alzheimer’s disease would be accelerated by agnostic, non-hypothesis-based biomarker discovery methods. There is a need for more complex contrasts and more complex mathematical models.

KEYWORDS:

• Alzheimer’s disease
• blood-based biomarkers
• Aptamarkers
• Aptamers

Declarations of Interest

NeoNeuro, the company that funded this manuscript, is a private company working to develop an improved blood-based diagnostic system for the prediction of brain amyloid status. NeoNeuro is wholly owned by NeoVentures Biotechnology Inc. (A Canadian registered private company). Gregory Penner and Ximena Vedoya own all shares in NeoVentures Biotechnology Inc. Gregory Penner has also received grant funding from GSK and has ownership over NeoNeuro. Ximena Vedoya has an ownership position over NeoNeuro. Soizic Lecocq and Anaëlle Chopin are employees of NeoNeuro. Simone Lista has received lecture honoraria from Roche. Harald Hampel serves as a Senior Associate Editor for the journal, ‘Alzheimer’s & Dementia’; has received lecture fees from Biogen, Roche, Eisai; has received research grants from Pfizer, Avid and MSD Avenir (paid to the institution); received travel funding from Functional Neuromodulation, Axovant, Eli Lilly and company, Takeda and Zinfandel, GE-Healthcare and Oryzon Genomics; received consultancy fees from Qynapse, Jung Diagnostics, Cytox Ltd., Axovant, Anavex, Takeda and Zinfandel, GE Healthcare and Oryzon Genomics, and Functional Neuromodulation; and has participated in scientific advisory boards of Functional Neuromodulation, Axovant, Eli Lilly and company, Cytox Ltd., GE Healthcare, Takeda and Zinfandel, Oryzon Genomics and Roche Diagnostics. Harald Hampel is supported by the AXA Research Fund, the ‘Foundation partenariale Sorbonne Universite’ and the ‘Fondation pour la Recherche sur Alzheimer’, Paris, France. Ce travail a bénéficie 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). Harald Hampel is co-inventor in the following patents as a scientific expert and has received no royalties:

• In vitro Multiparameter Determination Method for the Diagnosis and early diagnosis of Neurodegenerative Disorders Patent Number: 8,916,388.

• In vitro Procedure for Diagnosis and early Diagnosis of Neurodegenerative Diseases Patent Number: 8,298,784

• Neurodegenerative Markers for Psychiatric Conditions Publication Number: 20,120,196,300

• In vitro Multiparameter Determination Method for the Diagnosis and Early Diagnosis of Neurodegenerative Disorders Publication Number: 20,100,062,463

• In vitro Method for the Diagnosis and Early Diagnosis of Neurodegenerative Disorders Publication number: 20,100,035,286

• In vitro Method for the Diagnosis of Neurodegenerative Diseases Patent Number: 7,547,553

• CSF Diagnostic in Vitro Method for Diagnosis of Dementias and Neuroinflammatory Diseases Publication Number: 20,080,206,797

• In vitro Method for The Diagnosis of Neurodegenerative Diseases Publication Number: 20,080,199,966

• Neurodegenerative Markers for Psychiatric Conditions Publication Number: 20,080,131,921

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewers disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

The development of this manuscript was funded by NeoNeuro.