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Penner et al. Blood-based diagnostics of Alzheimer’s disease. Review paper.

Abstract: 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. 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.

Limiting putative biomarkers to those that have postulated role in the pathophysiology of the 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 contacts and more complex mathematical models.

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