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. 2022 Jul 12:13:890638.
doi: 10.3389/fneur.2022.890638. eCollection 2022.

Multi-Omics Interdisciplinary Research Integration to Accelerate Dementia Biomarker Development (MIRIADE)

Ekaterina Mavrina  1   2 , Leighann Kimble  1   2 , Katharina Waury  1   3 , Dea Gogishvili  1   3 , Nerea Gómez de San José  1   4 , Shreyasee Das  1   5 , Salomé Coppens  1   6 , Bárbara Fernandes Gomes  1   7 , Sára Mravinacová  1   8 , Anna Lidia Wojdała  1   9 , Katharina Bolsewig  1   10 , Sherif Bayoumy  1   10 , Felicia Burtscher  1   11 , Pablo Mohaupt  1   12 , Eline Willemse  1   10 , Charlotte Teunissen  1   10 ; MIRIADE consortium
Affiliations

Multi-Omics Interdisciplinary Research Integration to Accelerate Dementia Biomarker Development (MIRIADE)

Ekaterina Mavrina et al. Front Neurol. .

Abstract

Proteomics studies have shown differential expression of numerous proteins in dementias but have rarely led to novel biomarker tests for clinical use. The Marie Curie MIRIADE project is designed to experimentally evaluate development strategies to accelerate the validation and ultimate implementation of novel biomarkers in clinical practice, using proteomics-based biomarker development for main dementias as experimental case studies. We address several knowledge gaps that have been identified in the field. First, there is the technology-translation gap of different technologies for the discovery (e.g., mass spectrometry) and the large-scale validation (e.g., immunoassays) of biomarkers. In addition, there is a limited understanding of conformational states of biomarker proteins in different matrices, which affect the selection of reagents for assay development. In this review, we aim to understand the decisions taken in the initial steps of biomarker development, which is done via an interim narrative update of the work of each ESR subproject. The results describe the decision process to shortlist biomarkers from a proteomics to develop immunoassays or mass spectrometry assays for Alzheimer's disease, Lewy body dementia, and frontotemporal dementia. In addition, we explain the approach to prepare the market implementation of novel biomarkers and assays. Moreover, we describe the development of computational protein state and interaction prediction models to support biomarker development, such as the prediction of epitopes. Lastly, we reflect upon activities involved in the biomarker development process to deduce a best-practice roadmap for biomarker development.

Keywords: assay development; biomarkers; cerebrospinal fluid; dementia; immunoassays; implementation; mass spectrometry.

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Conflict of interest statement

SD is an employee of ADx NeuroSciences, Gent, Belgium. SC is an employee of National Measurement Laboratory at LGC, London, UK. CT has a collaboration contract with ADx Neurosciences, Quanterix, and Eli Lilly, performed contract research or received grants from AC-Immune, Axon Neurosciences, Bioconnect, Biogen, Brainstorm Therapeutics, Celgene, EIP Pharma, Eisai, PeopleBio, Quanterix, Roche, Toyama, and Vivoryon. She serves on editorial boards of Medidact Neurologie/Springer, Alzheimer Research and Therapy, Neurology: Neuroimmunology & Neuroinflammation, and is editor of a Neuromethods book Springer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Biomarker development workflow. ESR, Early stage researcher; MRM-MS, multiple reaction monitoring mass spectrometry; AD, Alzheimer's disease; FTD, frontotemporal dementia; DLB, dementia with Lewy bodies.
Figure 2
Figure 2
Schematic representation of the steps taken for biomarker selection in MIRIADE. CSF, cerebrospinal fluid.
See this image and copyright information in PMC

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