Multi-omics Interdisciplinary Research Integration to Address DEmentia diagnosis

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Deliverables

RUO label for two biomarker assays obtained

To comply with the directive 98/79/EC for RUO labelling, we will prepare the required technical documentation31 for the biomarker assays. The assays should comply with ISO 9001 guidelines. Moreover, the Intellectual Property (IP) rights should be secured. Also other legislation and regulatory affairs, should be secured before bringing assays to the market.

Harmonised calibrators and quality control reagents for ≥1 assay

Upscaled versions of the assays should be developed, for broader use. The quality of all reagents used for these assays should be extensively tested and documented according to CLSI criteria. We will initiate the validation in order to obtain the directive 98/79/EC for in vitro diagnostic (IVD) label, including development of harmonised standards and statistical approaches to optimise reagents in collaboration with LGC.

Report on clinical validation of 1-2 biomarkers per ESR (total 8-16 reports)

We will select a subset of CSF and blood samples from up to 100 people per clinical group (exact number will be adapted after power analysis for each assay) with uniform preanalytical protocols established in the BIOMARKAPD project for extended validation. Next, CSF and blood samples will be selected of patients in early dementia stages, such as Subjective Cognitive Decline (SCD) or Mild Cognitive Impairment (MCI). Extensive clinical information, such as clinical follow-up (>3 years of follow-up data available for listed patients), will be available for these samples. The group size will be informed by the proof of concept validation results (T2.3). Sample selection in this stage will be refined by the results of pre-analytical stability testing in T2.2 for the specific tests developed in WP2.Candidate biomarkers will be clinically validated in CSF and blood samples using assays and protocols developed in WP2. The candidate biomarkers will be measured in the available samples within the network and of the central biobank of BIOMARKAPD (Table 1.4) [28]. We will perform ROC analysis to infer the utility of each single biomarker in the diagnosis of AD, DLB and FTD and will study the biomarkers in relation to a specific pathology, e.g. TDP-43 inclusions in FTD. Added value to classical biomarkers (Abeta(42), (p)Tau) and relations with clinical severity data (e.g. MMSE, IADL scores) will be evaluated. Generalized linear mixed effects models will be applied to evaluate prognostic value, with different dementia diagnoses or severity at outcome variables. Results will be validated in external cohorts as ADNI (AD, MCI-CON) and the Swedish BIOFINDER Study (DLB, AD, other dementias, and controls).

Roadmap for collaborative biomarker discovery and data sharing

Informed by systematic literature review, ESR will study alternative workflows for biomarker development in a heterogeneous research network, their advantages and shortcoming. The ESR will conduct qualitative research (i.e. observation, interviews) on how different partners of the research network use alternative discovery processes, to what extent they complement each other and what challenges they entail (e.g.misalignments in data, underlying workflows). Next, we will perform comparative case studies of different segments of the MIRIADE network. For this, we will evaluate mechanisms to facilitate combination and orchestration of alternative development approaches across research groups. Lastly, we will develop a roadmap for the combination of complementary development processes that can be used by future biomarker development projects.

Analytically validated assays for 2-5 candidate biomarkers/ESR

The generated assays will be technically validated with regards to analytical sensitivity, specificity, spike-recovery and linearity according to consensus guidelines [27].

Initial clinical proof of concept for 1-2 assays/ESR (total 8-16 reports)

Initial proof of concept of the clinical use of the biomarker analysis by the generated immunoassays will be provided in small cohorts of clinical samples (e.g. n=20 per dementia type and subjects serving as controls) for CSF and blood. It is feasible that at least one assay per approach will be available at M18 (half way the project) for in-depth clinical validation in WP3.

Publications, in high rank scientific journals, in patient organisation newsletters and blogs

ESRs will be required to submit their results for poster and oral presentations to visit international conferences for mutual discussion of study results. In addition, every ESR project will prepare at least 3 manuscripts for peer-reviewed publication. This will again contribute to the training of the ESRs.

Doctoral degrees

All ESRs have obtained a doctoral degree.

Upscaled version of two assays validated according to regulatory standards

SOP for pre-analytics in blood assays

The pre-analytical stability of the novel biomarker tests need to be intensively studied. Pre-analytical SOPs have been standardised for CSF analysis32. Due to the higher cellular and protein contents relative to CSF, blood biomarker levels are strongly affected by differences in preanalytical protocols. Moreover, besides demographic factors (age, gender), lifestyle factors such as fasting status, excercise, can influence the results. Thus, for blood analysis of neurospecific proteins, and specifically for the targetted proteins, such SOPs need to be developed in order to get accurate and reproducible results, and studies to address all these pre-analytical factors should be design to provide a rationale for such SOPs.

Policy recommendations at the national and EU level

The project will start with a systematic literature review on academic data sharing, reuse and integration. Next, qualitative research will be conducted (i.e. interviews, observation) capturing organisational, social and institutional factors influencing data sharing, reuse and integration. Lastly, the ESR will perform a quantitative empirical survey on data sharing, reuse and integration practices in comparable research networks. Based on this, field experiments will be designed to evaluate mechanisms and tools that facilitate the reuse and integration of existing data and results as well as collection of novel data with future sharing and reuse in mind. Lastly, we will participate in policy workgroups (e.g., Knowledge Exchange on the European Level, national working groups) and prepare policy recommendations for research funders and organisations.

Online Dementia Disease Map

A comprehensive representation of disease mechanisms at the level of molecular processes will be developed, building a collection of interconnected signalling, metabolic and gene regulatory pathways relevant to dementia. The main steps are: i) using pathways from literature and reliable pathway databases (Reactome, PANTHER) with dementia customization; ii) develop consensus view by experts to ensure reprentation of disease hallmarks; iii) using inputs from text mining, protein-interactions databases and networks in BEL language to complete the reconstruction of mechanisms. The Dementia Disease Map will be developed in CellDesigner in the standard Systems Biology Graphical Notation using previously established protocols25. Maps will be accessible online via the MINERVA platform for advanced navigation, zooming and visualisation.

Presentations at international scientific conferences and patient meetings

ESR recruitment: All 15 ESRs are recruited; individual contracts are signed

Management and overall coordination by VUMC will enable MIRIADE activities in all work packages to be performed timely coherently and efficiently One of these activities will be coordination of ESR recruitment

Secondment coordination

We will coordinate secondments in terms of project progress (before secondment as well as during secondment), and make sure facilities are in place, arrange housing, etc..

Matrix-specific protein-antibody interaction prediction

The development of antibodies for novel proteins is based on best practices, instead of rational design, due to limited understanding of the exact state of the protein in a specific matrix. We will extend a protein-protein interaction method (SERENDIP26) to predict protein-antibody binding. Surface accessibility prediction for the different matrices will help to make the predictions matrix-specific. The algorithms will be trained by data on protein-antibody interactions in both CSF and blood, available from previous biomarker development efforts within the network (ISCIII), and from public data resources (HPA and DPB). The predictions will be experimentally validated by results of assay development in WP2; the surface accessibility predictions will be validated by HDX-MS analysis of protein conformational states in different biological matrices.

CSF/blood biomarker algorithms for the diagnosis of AD, DLB, FTD

We will develop specific algorithms for defining the biochemical signature of patients. Multivariate statistical methods will be applied, able to take into consideration the correlation structure of the data and the synergies and interactions existing among the potential biomarkers. Furthermore, we will investigate the use of machine learning approaches, such as clustering and deep learning, to develop robust classifiers. We will develop a classification scheme for FTD and DLB, similar to the A/T/N scheme for AD29. Results will be validated in independent cohorts listed in T3.2.

Inventory for patient perspectives: inventory results are reported and presented

A dynamic and interactive website will be developed, supporting blog services. The website will have a specific part dedicated for dialogue with patients and carers. An inventory will be held to obtain input on patient perspectives. These texts and the inventory will be developed in close collaboration with patient focus groups of the patient organisations and will be translated in a few main languages, e.g. German, to facilitate use of these sites across a broad public, including non-English speaking individuals.

Project website: The project website (intranet as well as internet) is up and running

Secure efficient internal communication within the MIRIADE consortium

Publications

Analytical and clinical validation of a blood progranulin ELISA in frontotemporal dementias

Author(s): Francisco Meda, Joel Simrén, Barbara Borroni, Valentina Cantoni, Silvana Archetti, Giorgio Biasiotto, Ulf Andreasson, Kaj Blennow, Hlin Kvartsberg, Henrik Zetterberg
Published in: Clinical Chemistry and Laboratory Medicine (CCLM), Issue 61, 2023, Page(s) 2195-2204, ISSN 1434-6621
Publisher: Walter de Gruyter GmbH & Co. KG
DOI: 10.1515/cclm-2023-0562

Glutamate receptor 4 as a fluid biomarker for the diagnosis of psychiatric disorders

Author(s): Nerea Gómez de San José, Julie Goossens, Mhd Rami Al Shweiki, Steffen Halbgebauer, Patrick Oeckl, Petra Steinacker, Karin M. Danzer, Heiko Graf, Carlos Schönfeldt-Lecuona, Olivia Belbin, Alberto Lleó, Eugeen Vanmechelen, Markus Otto
Published in: Journal of Psychiatric Research, Issue 156, 2023, Page(s) 390-397, ISSN 0022-3956
Publisher: Pergamon Press Ltd.
DOI: 10.1016/j.jpsychires.2022.10.010

Ten quick tips for sequence-based prediction of protein properties using machine learning

Author(s): Qingzhen Hou, Katharina Waury, Dea Gogishvili, K. Anton Feenstra
Published in: PLOS Computational Biology, Issue 18, 2022, Page(s) e1010669, ISSN 1553-7358
Publisher: Public Library of Science
DOI: 10.1371/journal.pcbi.1010669

A Combination of Neurofilament Light, Glial Fibrillary Acidic Protein, and Neuronal Pentraxin-2 Discriminates Between Frontotemporal Dementia and Other Dementias

Author(s): Katharina Bolsewig, Yanaika S. Hok-A-Hin, Federica N. Sepe, Lynn Boonkamp, Dirk Jacobs, Giovanni Bellomo, Federico Paolini Paoletti, Eugeen Vanmechelen, Charlotte E. Teunissen, Lucilla Parnetti, Eline A. J. Willemse
Published in: Journal of Alzheimer's Disease, Issue 90, 2022, Page(s) 363-380, ISSN 1387-2877
Publisher: IOS Press
DOI: 10.3233/jad-220318

A cell-free high throughput assay for assessment of SARS-CoV-2 neutralizing antibodies

Author(s): Sara Mravinacova, Malin Jönsson, Wanda Christ, Jonas Klingström, Jamil Yousef, Cecilia Hellström, My Hedhammar, Sebastian Havervall, Charlotte Thålin, Elisa Pin, Hanna Tegel, Peter Nilsson, Anna Månberg, Sophia Hober
Published in: New Biotechnology, 2022, ISSN 1871-6784
Publisher: Elsevier BV
DOI: 10.1016/j.nbt.2021.10.002

Development of an ultrasensitive microfluidic assay for the analysis of Glial fibrillary acidic protein (GFAP) in blood

Author(s): Badrieh Fazeli, André Huss, Nerea Gómez de San José, Markus Otto, Hayrettin Tumani, Steffen Halbgebauer
Published in: Frontiers in Molecular Biosciences, Issue 10, 2023, ISSN 2296-889X
Publisher: Frontiers Media S.A.
DOI: 10.3389/fmolb.2023.1175230

Association of Plasma p-tau181 and p-tau231 Concentrations With Cognitive Decline in Patients With Probable Dementia With Lewy Bodies

Author(s): Maria C Gonzalez, Nicholas J Ashton, Bárbara Fernandes Gomes, Diego Alejandro Tovar-Rios, Frédéric Blanc, Thomas K Karikari, Brit Mollenhauer, Andrea Pilotto, Afina Lemstra, Claire Paquet, Carla Abdelnour, Milica G Kramberger, Laura Bonanni, Rik Vandenberghe, Abdul Hye, Kaj Blennow, Henrik Zetterberg, Dag Aarsland, European–Dementia With Lewy Bodies (E-DLB) Consortium
Published in: JAMA Neurology, 2022, ISSN 2168-6149
Publisher: American Medical Association
DOI: 10.1001/jamaneurol.2021.4222

CSF and plasma Aβ42/40 across Alzheimer’s disease continuum: comparison of two ultrasensitive Simoa<sup>®</sup> assays targeting distinct amyloid regions

Author(s): Anna Lidia Wojdała, Giovanni Bellomo, Andrea Toja, Lorenzo Gaetani, Lucilla Parnetti, Davide Chiasserini
Published in: Clinical Chemistry and Laboratory Medicine (CCLM), Issue 62, 2024, Page(s) 332-340, ISSN 1434-6621
Publisher: Walter de Gruyter GmbH & Co. KG
DOI: 10.1515/cclm-2023-0659

Phosphorylated tau181 in plasma as a potential biomarker for Alzheimer's disease in adults with Down syndrome

Author(s): Alberto Lleó, Henrik Zetterberg, Jordi Pegueroles, Thomas K Karikari, María Carmona-Iragui, Nicholas J Ashton, Victor Montal, Isabel Barroeta, Juan Lantero-Rodríguez, Laura Videla, Miren Altuna, Bessy Benejam, Susana Fernandez, Silvia Valldeneu, Diana Garzón, Alexandre Bejanin, Maria Florencia Iulita, Valle Camacho, Santiago Medrano-Martorell, Olivia Belbin, Jordi Clarimon, Sylvain Lehmann, Da
Published in: Nature Communications, 2021, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-021-24319-x

α-Synuclein seed amplification assay as a diagnostic tool for parkinsonian disorders

Author(s): Bárbara Fernandes Gomes, Carly M. Farris, Yihua Ma, Luis Concha-Marambio, Russ Lebovitz, Bengt Nellgård, Keti Dalla, Julius Constantinescu, Radu Constantinescu, Johan Gobom, Ulf Andreasson, Henrik Zetterberg, Kaj Blennow
Published in: Parkinsonism & Related Disorders, Issue 117, 2023, Page(s) 105807, ISSN 1353-8020
Publisher: Elsevier BV
DOI: 10.1016/j.parkreldis.2023.105807

Neurofilament light protein as a biomarker for spinal muscular atrophy: a review and reference ranges

Author(s): Sherif Bayoumy, Inge M.W. Verberk, Lisa Vermunt, Eline Willemse, Ben den Dulk, Ans T. van der Ploeg, Dasja Pajkrt, Elisa Nitz, Johanna M.P. van den Hout, Julie van der Post, Nicole I. Wolf, Shanice Beerepoot, Ewout J.N. Groen, Victoria Tüngler, Charlotte E. Teunissen
Published in: Clinical Chemistry and Laboratory Medicine (CCLM), Issue 62, 2024, Page(s) 1252-1265, ISSN 1434-6621
Publisher: Walter de Gruyter GmbH & Co. KG
DOI: 10.1515/cclm-2023-1311

Potential diagnostic value of CSF metabolism-related proteins across the Alzheimer’s disease continuum

Author(s): Silvia Paciotti, Anna Lidia Wojdała, Giovanni Bellomo, Andrea Toja, Elena Chipi, Sander R. Piersma, Thang V. Pham, Lorenzo Gaetani, Connie R. Jimenez, Lucilla Parnetti, Davide Chiasserini
Published in: Alzheimer's Research & Therapy, Issue 15, 2023, ISSN 1758-9193
Publisher: BioMed Central
DOI: 10.1186/s13195-023-01269-8

Readthrough isoform of aquaporin-4 (AQP4) as a therapeutic target for Alzheimer’s disease and other proteinopathies

Author(s): Pablo Mohaupt, Jérôme Vialaret, Christophe Hirtz, Sylvain Lehmann
Published in: Alzheimer's Research & Therapy, Issue 15, 2023, ISSN 1758-9193
Publisher: BioMed Central
DOI: 10.1186/s13195-023-01318-2

Investigating alpha‐synuclein co‐pathology in Alzheimer's disease by means of cerebrospinal fluid alpha‐synuclein seed amplification assay

Author(s): Giovanni Bellomo, Andrea Toja, Federico Paolini Paoletti, Yihua Ma, Carly M. Farris, Lorenzo Gaetani, Nicola Salvadori, Davide Chiasserini, Anna Lidia Wojdaƚa, Luis Concha‐Marambio, Lucilla Parnetti
Published in: Alzheimer's & Dementia, Issue 20, 2024, Page(s) 2444-2452, ISSN 1552-5260
Publisher: Elsevier BV
DOI: 10.1002/alz.13658

CSF protein ratios with enhanced potential to reflect Alzheimer’s disease pathology and neurodegeneration

Author(s): Sára Mravinacová, Vilma Alanko, Sofia Bergström, Claire Bridel, Yolande Pijnenburg, Göran Hagman, Miia Kivipelto, Charlotte Teunissen, Peter Nilsson, Anna Matton, Anna Månberg
Published in: Molecular Neurodegeneration, Issue 19, 2024, ISSN 1750-1326
Publisher: BioMed Central
DOI: 10.1186/s13024-024-00705-z

Methods to Discover and Validate Biofluid-Based Biomarkers in Neurodegenerative Dementias

Author(s): Charlotte E. Teunissen, Leighann Kimble, Sherif Bayoumy, Katharina Bolsewig, Felicia Burtscher, Salomé Coppens, Shreyasee Das, Dea Gogishvili, Bárbara Fernandes Gomes, Nerea Gómez de San José, Ekaterina Mavrina, Francisco J. Meda, Pablo Mohaupt, Sára Mravinacová, Katharina Waury, Anna Lidia Wojdała, Sanne Abeln, Davide Chiasserini, Christophe Hirtz, Lorenzo Gaetani, Lisa Vermunt, Giovanni B
Published in: Molecular & Cellular Proteomics, Issue 22, 2024, Page(s) 100629, ISSN 1535-9476
Publisher: American Society for Biochemistry and Molecular Biology Inc.
DOI: 10.1016/j.mcpro.2023.100629

Discovery of novel CSF biomarkers to predict progression in dementia using machine learning

Author(s): Dea Gogishvili, Eleonora M. Vromen, Sascha Koppes-den Hertog, Afina W. Lemstra, Yolande A. L. Pijnenburg, Pieter Jelle Visser, Betty M. Tijms, Marta Del Campo, Sanne Abeln, Charlotte E. Teunissen, Lisa Vermunt
Published in: Scientific Reports, Issue 13, 2023, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-023-33045-x

Cerebrospinal fluid biomarkers and cognitive trajectories in patients with Alzheimer’s disease and a history of traumatic brain injury

Author(s): Suzan van Amerongen, Shreyasee Das, Suzie Kamps, Julie Goossens, Bram Bongers, Yolande A.L. Pijnenburg, Eugeen Vanmechelen, Everard G.B. Vijverberg, Charlotte E. Teunissen, Inge M.W. Verberk
Published in: Neurobiology of Aging, Issue 141, 2024, Page(s) 121-128, ISSN 0197-4580
Publisher: Elsevier BV
DOI: 10.1016/j.neurobiolaging.2024.06.001

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

Author(s): Ekaterina Mavrina, Leighann Kimble, Katharina Waury, Dea Gogishvili, Nerea Gómez de San José, Shreyasee Das, Salomé Coppens, Bárbara Fernandes Gomes, Sára Mravinacová, Anna Lidia Wojdała, Katharina Bolsewig, Sherif Bayoumy, Felicia Burtscher, Pablo Mohaupt, Eline Willemse, Charlotte Teunissen, null null
Published in: Frontiers in Neurology, Issue 13, 2022, ISSN 1664-2295
Publisher: Frontiers Research Foundation
DOI: 10.3389/fneur.2022.890638

Exploring the brain metabolic correlates of process-specific CSF biomarkers in patients with MCI due to Alzheimer's disease: preliminary data

Author(s): Federico Massa, Steffen Halbgebauer, Lorenzo Barba, Patrick Oeckl, Nerea Gómez de San José, Matteo Bauckneht, Francesco Lanfranchi, Tiziana Vigo, Dario Arnaldi, Matteo Pardini, Silvia Morbelli, Andrea Chincarini, Henryk Barthel, Markus Otto, Flavio Nobili
Published in: Neurobiology of Aging, Issue 117, 2024, Page(s) 212-221, ISSN 0197-4580
Publisher: Elsevier BV
DOI: 10.1016/j.neurobiolaging.2022.03.019

The use of synaptic biomarkers in cerebrospinal fluid to differentiate behavioral variant of frontotemporal dementia from primary psychiatric disorders and Alzheimer’s disease

Author(s): Shreyasee Das, Marie-Paule E. van Engelen, Julie Goossens, Dirk Jacobs, Bram Bongers, Jay L. P. Fieldhouse, Yolande A. L. Pijnenburg, Charlotte E. Teunissen, Eugeen Vanmechelen, Inge M. W. Verberk
Published in: Alzheimer's Research & Therapy, Issue 16, 2024, ISSN 1758-9193
Publisher: BioMed Central
DOI: 10.1186/s13195-024-01409-8

Deciphering Protein Secretion from the Brain to Cerebrospinal Fluid for Biomarker Discovery

Author(s): Katharina Waury, Renske de Wit, Inge M. W. Verberk, Charlotte E. Teunissen, Sanne Abeln
Published in: Journal of Proteome Research, Issue 22, 2023, Page(s) 3068-3080, ISSN 1535-3893
Publisher: American Chemical Society
DOI: 10.1021/acs.jproteome.3c00366

Fully automated measurement of plasma Aβ42/40 and p‐tau181: Analytical robustness and concordance with cerebrospinal fluid profile along the Alzheimer's disease continuum in two independent cohorts

Author(s): Giovanni Bellomo, Sherif Bayoumy, Alfredo Megaro, Andrea Toja, Giovanna Nardi, Lorenzo Gaetani, Elena R. Blujdea, Federico Paolini Paoletti, Anna Lidia Wojdaƚa, Davide Chiasserini, Wiesje M. van der Flier, Inge M. W. Verberk, Charlotte Teunissen, Lucilla Parnetti
Published in: Alzheimer's & Dementia, Issue 20, 2024, Page(s) 2453-2468, ISSN 1552-5260
Publisher: Elsevier BV
DOI: 10.1002/alz.13687

Trajectories of CSF and plasma biomarkers across Alzheimer's disease continuum: disease staging by NF-L, p-tau181, and GFAP

Author(s): Anna Lidia Wojdała, Giovanni Bellomo, Lorenzo Gaetani, Andrea Toja, Elena Chipi, Dandan Shan, Davide Chiasserini, Lucilla Parnetti
Published in: Neurobiology of Disease, Issue 189, 2023, Page(s) 106356, ISSN 0969-9961
Publisher: Academic Press
DOI: 10.1016/j.nbd.2023.106356

Phosphatidylethanolamine Binding Protein 1 (PEBP1) in Alzheimer’s Disease: ELISA Development and Clinical Validation

Author(s): Anna Lidia Wojdała, Davide Chiasserini, Giovanni Bellomo, Silvia Paciotti, Lorenzo Gaetani, Federico Paolini Paoletti, Lucilla Parnetti
Published in: Journal of Alzheimer's Disease, Issue 88, 2023, Page(s) 1459-1468, ISSN 1387-2877
Publisher: IOS Press
DOI: 10.3233/jad-220323

Neurofilament-Light, a Promising Biomarker: Analytical, Metrological and Clinical Challenges

Author(s): Salomé Coppens, Sylvain Lehmann, Christopher Hopley, Christophe Hirtz
Published in: International Journal of Molecular Sciences, Issue 24, 2023, Page(s) 11624, ISSN 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms241411624

The alternative proteome in neurobiology

Author(s): Pablo Mohaupt, Xavier Roucou, Constance Delaby, Jérôme Vialaret, Sylvain Lehmann, Christophe Hirtz
Published in: Frontiers in Cellular Neuroscience, Issue 16, 2022, ISSN 1662-5102
Publisher: Frontiers Research Foundation
DOI: 10.3389/fncel.2022.1019680

Neurofilament light oligomers in neurodegenerative diseases: quantification by homogeneous immunoassay in cerebrospinal fluid

Author(s): Francisco J. Meda, Kathryn Knowles, Imogen J. Swift, Aitana Sogorb-Esteve, Jonathan D. Rohrer, Anna Dittrich, Ingmar Skoog, Silke Kern, Bruno Becker, Kaj Blennow, Ulf Andreasson, Hlin Kvartsberg, Henrik Zetterberg
Published in: BMJ Neurology Open, Issue 5, 2024, Page(s) e000395, ISSN 2632-6140
Publisher: British Medical Association
DOI: 10.1136/bmjno-2022-000395

Use of plasma biomarkers for AT(N) classification of neurodegenerative dementias

Author(s): Daniel Alcolea, Constance Delaby, Laia Muñoz, Soraya Torres, Teresa Estellés, Nuole Zhu, Isabel Barroeta , María Carmona-Iragui, Ignacio Illán-Gala, Miguel Ángel Santos-Santos, Miren Altuna, Isabel Sala, Mª Belén Sánchez-Saudinós, Laura Videla, Sílvia Valldeneu, Andrea Subirana, Jordi Pegueroles, Christophe Hirtz, Jérôme Vialaret, Sylvain Lehmann, Thomas K Karikari, Nicholas J Ashton,
Published in: Journal of Neurology, Neurosurgery and Psychiatry, 2021, ISSN 0022-3050
Publisher: BMJ Publishing Group
DOI: 10.1136/jnnp-2021-326603

β-Synuclein as a candidate blood biomarker for synaptic degeneration in Alzheimer’s disease

Author(s): Pablo Mohaupt, Marie-Laure Pons, Jérôme Vialaret, Constance Delaby, Christophe Hirtz, Sylvain Lehmann
Published in: Alzheimer's Research & Therapy, Issue 14, 2022, ISSN 1758-9193
Publisher: BioMed Central
DOI: 10.1186/s13195-022-01125-1

Caregivers’ attitudes toward blood‐based biomarker testing for Alzheimer's disease

Author(s): Katharina Bolsewig, Hester Blok, Eline A. J. Willemse, Rob B. M. Groot Zwaaftink, Minke Kooistra, Ellen M. A. Smets, Charlotte E. Teunissen, Leonie N. C. Visser
Published in: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, Issue 16, 2024, ISSN 2352-8729
Publisher: Wiley Periodicals LLC
DOI: 10.1002/dad2.12549

Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration

Author(s): Nerea Gómez de San José; Federico Massa; Steffen Halbgebauer; Patrick Oeckl; Petra Steinacker; Markus Otto
Published in: Neural Transmission, 2021, ISSN 0300-9564
Publisher: Springer Verlag
DOI: 10.1007/s00702-021-02411-2

Proteome encoded determinants of protein sorting into extracellular vesicles

Author(s): Katharina Waury, Dea Gogishvili, Rienk Nieuwland, Madhurima Chatterjee, Charlotte E. Teunissen, Sanne Abeln
Published in: Journal of Extracellular Biology, Issue 3, 2024, ISSN 2768-2811
Publisher: Wiley Periodicals, LLC
DOI: 10.1002/jex2.120

Synaptic biomarkers in the cerebrospinal fluid associate differentially with classical neuronal biomarkers in patients with Alzheimer’s disease and frontotemporal dementia

Author(s): Shreyasee Das, Julie Goossens, Dirk Jacobs, Nele Dewit, Yolande A. L. Pijnenburg, Sjors G. J. G. In ‘t Veld, Charlotte E. Teunissen, Eugeen Vanmechelen
Published in: Alzheimer's Research & Therapy, Issue 15, 2023, ISSN 1758-9193
Publisher: BioMed Central
DOI: 10.1186/s13195-023-01212-x

How sticky are our proteins? Quantifying hydrophobicity of the human proteome

Author(s): Juami Hermine Mariama van Gils, Dea Gogishvili, Jan van Eck, Robbin Bouwmeester, Erik van Dijk, Sanne Abeln
Published in: Bioinformatics Advances, Issue 2, 2022, ISSN 2635-0041
Publisher: Oxford University Press
DOI: 10.1093/bioadv/vbac002

Increasing the sensitivity of Simoa via bead count reduction facilitates the quantification of pTau‐181 in dried plasma spots

Author(s): Pablo Mohaupt, Jérôme Vialaret, Christophe Hirtz, Sylvain Lehmann
Published in: Alzheimer's & Dementia: Translational Research & Clinical Interventions, Issue 10, 2024, ISSN 2352-8737
Publisher: Elsevier Inc.
DOI: 10.1002/trc2.12456

Structural flexibility and heterogeneity of recombinant human glial fibrillary acidic protein (GFAP)

Author(s): Dea Gogishvili, Eva Illes‐Toth, Matthew J. Harris, Christopher Hopley, Charlotte E. Teunissen, Sanne Abeln
Published in: Proteins: Structure, Function, and Bioinformatics, Issue 92, 2024, Page(s) 649-664, ISSN 0887-3585
Publisher: Wiley-Liss Inc
DOI: 10.1002/prot.26656

Association of Plasma Amyloid, P-Tau, GFAP, and NfL With CSF, Clinical, and Cognitive Features in Patients With Dementia With Lewy Bodies

Author(s): Katharina Bolsewig, Annemartijn A.J.M. van Unnik, Elena R. Blujdea, Maria C. Gonzalez, Nicholas J. Ashton, Dag Aarsland, Henrik Zetterberg, Alessandro Padovani, Laura Bonanni, Brit Mollenhauer, Sebastian Schade, Rik Vandenberghe, Koen Poesen, Milica G. Kramberger, Claire Paquet, Olivier Bousiges, Benjamin Cretin, Eline A.J. Willemse, Charlotte E. Teunissen, Afina W. Lemstra, null null
Published in: Neurology, Issue 102, 2024, ISSN 0028-3878
Publisher: Lippincott Williams & Wilkins Ltd.
DOI: 10.1212/wnl.0000000000209418

Cerebrospinal fluid lipoproteins inhibit α-synuclein aggregation by interacting with oligomeric species in seed amplification assays

Author(s): Giovanni Bellomo, Silvia Paciotti, Luis Concha-Marambio, Domenico Rizzo, Anna Lidia Wojdaƚa, Davide Chiasserini, Leonardo Gatticchi, Linda Cerofolini, Stefano Giuntini, Chiara Maria Giulia De Luca, Yihua Ma, Carly M. Farris, Giuseppe Pieraccini, Sara Bologna, Marta Filidei, Enrico Ravera, Moreno Lelli, Fabio Moda, Marco Fragai, Lucilla Parnetti, Claudio Luchinat
Published in: Molecular Neurodegeneration, Issue 18, 2023, ISSN 1750-1326
Publisher: BioMed Central
DOI: 10.1186/s13024-023-00613-8

Association of Apolipoprotein E ɛ4 Allele With Clinical and Multimodal Biomarker Changes of Alzheimer Disease in Adults With Down Syndrome

Author(s): Alexandre Bejanin, Maria Florencia Iulita, Eduard Vilaplana, Maria Carmona-Iragui, Bessy Benejam, Laura Videla, Isabel Barroeta, Susana Fernandez, Miren Altuna, Jordi Pegueroles, Victor Montal, Silvia Valldeneu, Sandra Giménez, Sofía González-Ortiz, Laia Muñoz, Concepción Padilla, Mateus Rozalem Aranha, Teresa Estellés, Ignacio Illán-Gala, Olivia Belbin, Valle Camacho, Liam Reese Wilson, Ti
Published in: JAMA Neurology, 2021, ISSN 2168-6149
Publisher: American Medical Association
DOI: 10.1001/jamaneurol.2021.1893

Subsequent correlated changes in complement component 3 and amyloid beta oligomers in the blood of patients with Alzheimer's disease

Author(s): Kyu Hwan Shim, Danyeong Kim, Min Ju Kang, Jung‐Min Pyun, Young Ho Park, Young Chul Youn, Kyung Won Park, Kyoungho Suk, Ho‐Won Lee, Bárbara Fernandes Gomes, Henrik Zetterberg, Seong Soo A. An, SangYun Kim, null null
Published in: Alzheimer's & Dementia, Issue 20, 2024, Page(s) 2731-2741, ISSN 1552-5260
Publisher: Elsevier BV
DOI: 10.1002/alz.13734

Bioinformatics tools and data resources for assay development of fluid protein biomarkers

Author(s): Katharina Waury, Eline A. J. Willemse, Eugeen Vanmechelen, Henrik Zetterberg, Charlotte E. Teunissen, Sanne Abeln
Published in: Biomarker Research, Issue 10, 2022, ISSN 2050-7771
Publisher: Springer Science and Business Media LLC
DOI: 10.1186/s40364-022-00425-w

Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview.

Author(s): Constance Delaby, Charlotte E Teunissen, Kaj Blennow, Daniel Alcolea, Ivan Arisi, Elodie Bouaziz Amar, Anne Beaume, Aurélie Bedel, Giovanni Bellomo, Edith Bigot-Corbel, Maria Bjerke, Marie-Céline Blanc-Quintin, Mercè Boada, Olivier Bousiges, Miles D Chapman, Mari L DeMarco, Mara D'Onofrio, Julien Dumurgier, Diane Dufour-Rainfray, Sebastiaan Engelborghs, Hermann Esselmann, Anne Fogli, Audrey Gab
Published in: Alzheimer’s and Dementia, 2021, ISSN 1552-5279
Publisher: John Wiley & Sons, Ltd
DOI: 10.1002/alz.12545

Characterization of pre-analytical sample handling effects on a panel of Alzheimer's disease-related blood-based biomarkers: Results from the Standardization of Alzheimer's Blood Biomarkers (SABB) working group.

Author(s): Inge M W Verberk, Els O Misdorp, Jannet Koelewijn, Andrew J Ball, Kaj Blennow, Jeffrey L Dage, Noelia Fandos, Oskar Hansson, Christophe Hirtz, Shorena Janelidze, Sungmin Kang, Kristopher Kirmess, Jana Kindermans, Ryan Lee, Matthew R Meyer, Dandan Shan, Leslie M Shaw, Teresa Waligorska, Tim West, Henrik Zetterberg, Rebecca M Edelmayer, Charlotte E Teunissen
Published in: Alzheimer’s and Dementia, 2021, ISSN 1552-5279
Publisher: John Wiley & Sons, Ltd
DOI: 10.1002/alz.12510

Clinical and analytical comparison of six Simoa assays for plasma P-tau isoforms P-tau181, P-tau217 and P-tau231

Author(s): Sherif Bayoumy, Inge M W Verberk, Ben den Dulk, Zulaiga Hussainali, Marissa Zwan, Wiesje M van der Flier, Nicholas J Ashton, Henrik Zetterberg, Kaj Blennow, Jeroen Vanbrabant, Erik Stoops, Eugeen Vanmechelen, Jeffrey L Dage, Charlotte E Teunissen
Published in: Alzheimer's Research & Therapy, 2021, ISSN 1758-9193
Publisher: BioMed Central
DOI: 10.1186/s13195-021-00939-9

Clinical and analytical comparison of three assays for plasma p-tau isoforms on an ultrasensitive platform

Author(s): Sherif Bayoumy, Ben Den Dulk, Zulaiga Hussainali, Inge M.W. Verberk, Wiesje M van der Flier, Marissa D. Zwan, Jeffrey L. Dage, Charlotte E. Teunissen
Published in: Alzheimer’s and Dementia, 2021
Publisher: John Wiley & Sons, Ltd
DOI: 10.1002/alz.054044

Addressing inter-individual variability in CSF levels of brain-derived proteins across neurodegenerative diseases

Author(s): Sára Mravinacová, Sofia Bergström, Jennie Olofsson, Nerea Gómez de San José, Sarah Anderl-Straub, Janine Diehl-Schmid, Klaus Fassbender, Klaus Fliessbach, Holger Jahn, Johannes Kornhuber, G. Bernhard Landwehrmeyer, Martin Lauer, Johannes Levin, Albert C. Ludolph, Johannes Prudlo, Anja Schneider, Matthias L. Schroeter, Jens Wiltfang, Petra Steinacker, Markus Otto, Peter Nilsson, Anna Månberg,
Published in: Issue 27-05-2024, 2024
Publisher: Cold Spring Harbor Laboratory
DOI: 10.1101/2024.05.27.24307739

Targeting multiphosphorylated tau: technical and clinical validation of a new Simoa® assay for CSF and plasma detection of tau simultaneously phosphorylated at T181 and T231

Author(s): Anna Lidia Wojdała, Giovanni Bellomo, Lorenzo Gaetani, Dandan Shan, Lucilla Parnetti, Davide Chiasserini
Published in: 2024
Publisher: Cold Spring Harbor Laboratory
DOI: 10.1101/2023.06.08.23291128

Comparison of sequence- and structure-based antibody clustering approaches on simulated repertoire sequencing data

Author(s): Katharina Waury, Stefan H. Lelieveld, Sanne Abeln, Henk-Jan van den Ham
Published in: Issue 13-06-2024, 2024
Publisher: Cold Spring Harbor Laboratory
DOI: 10.1101/2024.06.11.598449

Cerebrospinal fluid levels of NfM in relation to NfL and pNfH as prognostic markers in amyotrophic lateral sclerosis

Author(s): Jennie Olofsson, Sofia Bergström, Sára Mravinacová, Ulf Kläppe, Linn Öijerstedt, Henrik Zetterberg, Kaj Blennow, Caroline Ingre, Peter Nilsson, Anna Månberg
Published in: Issue 10-07-2024, 2024
Publisher: Cold Spring Harbor Laboratory
DOI: 10.1101/2024.07.09.24310135

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