The EPND cohort: study design and CSF proteomics across Alzheimer’s disease, dementia with Lewy bodies, and Parkinson’s disease

The development of treatments for Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and Parkinson’s disease (PD) is hampered by the scarce understanding of disease-specific and shared pathophysiological mechanisms. Cohorts covering AD, DLB, and PD with multiple, harmonized in vivo biomarkers of both established pathology and broader molecular processes are scarce, limiting comparisons across diseases. Therefore, we set up the European Platform for Neurodegenerative Diseases (EPND) cohort. Here, we describe its design and methods. Additionally, we explore disease-specific and shared cerebrospinal fluid (CSF) proteomic changes across diseases. To build the EPND cohort, participants with AD, DLB, PD, or controls were selected from ten European cohorts. Samples were centrally analysed. Amyloid-β (Aβ) 42, Aβ40, phosphorylated tau (​​p-tau) 181, and neurofilament light were measured in CSF and plasma, and total α-synuclein in CSF (all using Elecsys). Complement assays were performed in CSF (Milliplex) and plasma (SVAR), and proteomics panels (Olink Explore 3072, SomaScan 7k) were measured in CSF. Cohort data on demographics, clinical information, cognition, rating scales, lifestyle, genetics, and key imaging measures were centrally harmonized. Using this cohort, we explored CSF proteins ( n = 1617) uniquely and commonly dysregulated across diseases, measured by Olink proximity extension assays. Data were analyzed by linear regression adjusted for age, sex, and mean CSF protein level (average z-scored level of all highly detected Olink proteins). P-values were FDR-corrected. 353 participants were included (age 67.1 [SD 9.2], 133 [38%] female) in the EPND cohort, of which 151 with AD, 67 with DLB, 75 with PD, 57 controls, and 3 with other diagnoses. Sample analyses and data harmonization generated five datasets, which can be requested​ through the EPND Catalogue for research reuse. Exploratory proteomic analyses in a subset (325 participants) revealed CSF proteins specifically dysregulated in AD ( n = 9), DLB ( n = 1), or PD ( n = 2), as well as proteins similarly dysregulated across AD and DLB ( n = 10) and across DLB and PD ( n = 4), but not across AD and PD. The EPND cohort represents a valuable resource for neurodegenerative disease research, covering AD, DLB, and PD with centrally measured targeted and high-plex biomarkers. Available for research reuse via the EPND Catalogue, this cohort supports collaborative studies across neurodegenerative diseases. Current and future results will provide insights into disease-specific and common pathophysiological mechanisms and inform trial designs.

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Journal
Alzheimer s Research & Therapy
Published
2026-11-11
DOI
https://doi.org/10.1186/s13195-026-02251-w
Primary Topic
Dementia and Cognitive Impairment Research
Type
article
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article

The EPND cohort: study design and CSF proteomics across Alzheimer’s disease, dementia with Lewy bodies, and Parkinson’s disease

Emrah Düzel, Kathrin Brockmann, Zuzana Nedelská, Anna Pramhed et al.
Alzheimer s Research & Therapy
Dementia and Cognitive Impairment Research
article

The EPND cohort: study design and CSF proteomics across Alzheimer’s disease, dementia with Lewy bodies, and Parkinson’s disease

Emrah Düzel, Kathrin Brockmann, Zuzana Nedelská, Anna Pramhed, Annika E. Spottke, Gabor C. Petzold, Pieter Jelle Visser, Betty Marije Tijms, Afina Willemina Lemstra, Dag Aarsland, Mikhail N. Levit, Frank Jessen, Ann-Cecilie Hopøy, Rajaraman Krishnan, Tormod Fladby, Thomas Gasser, Davit Chokoshvili, Stephanie J. B. Vos, Sophie Mutel, Charlotte Elisabeth Teunissen, Anja Schneider, Aurore Delvenne, Gwendlyn Kollmorgen, Jakub Hort, Maarten Timmers, Pavithra Krishnaswami, Clara Quijano‐Rubio, Marianna Rizzo, Giovanni B. Frisoni, Henrik Zetterberg, Rejko Krüger, Jort Vijverberg, Sara B. G. Fernandes, Günter U. Höglinger, Fredric Brosseron, Michele T. Hu
article en

Abstract

The development of treatments for Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and Parkinson’s disease (PD) is hampered by the scarce understanding of disease-specific and shared pathophysiological mechanisms. Cohorts covering AD, DLB, and PD with multiple, harmonized in vivo biomarkers of both established pathology and broader molecular processes are scarce, limiting comparisons across diseases. Therefore, we set up the European Platform for Neurodegenerative Diseases (EPND) cohort. Here, we describe its design and methods. Additionally, we explore disease-specific and shared cerebrospinal fluid (CSF) proteomic changes across diseases. To build the EPND cohort, participants with AD, DLB, PD, or controls were selected from ten European cohorts. Samples were centrally analysed. Amyloid-β (Aβ) 42, Aβ40, phosphorylated tau (​​p-tau) 181, and neurofilament light were measured in CSF and plasma, and total α-synuclein in CSF (all using Elecsys). Complement assays were performed in CSF (Milliplex) and plasma (SVAR), and proteomics panels (Olink Explore 3072, SomaScan 7k) were measured in CSF. Cohort data on demographics, clinical information, cognition, rating scales, lifestyle, genetics, and key imaging measures were centrally harmonized. Using this cohort, we explored CSF proteins ( n = 1617) uniquely and commonly dysregulated across diseases, measured by Olink proximity extension assays. Data were analyzed by linear regression adjusted for age, sex, and mean CSF protein level (average z-scored level of all highly detected Olink proteins). P-values were FDR-corrected. 353 participants were included (age 67.1 [SD 9.2], 133 [38%] female) in the EPND cohort, of which 151 with AD, 67 with DLB, 75 with PD, 57 controls, and 3 with other diagnoses. Sample analyses and data harmonization generated five datasets, which can be requested​ through the EPND Catalogue for research reuse. Exploratory proteomic analyses in a subset (325 participants) revealed CSF proteins specifically dysregulated in AD ( n = 9), DLB ( n = 1), or PD ( n = 2), as well as proteins similarly dysregulated across AD and DLB ( n = 10) and across DLB and PD ( n = 4), but not across AD and PD. The EPND cohort represents a valuable resource for neurodegenerative disease research, covering AD, DLB, and PD with centrally measured targeted and high-plex biomarkers. Available for research reuse via the EPND Catalogue, this cohort supports collaborative studies across neurodegenerative diseases. Current and future results will provide insights into disease-specific and common pathophysiological mechanisms and inform trial designs.

Alzheimer s Research & Therapy
University of Geneva (CH), University of Bonn (DE), University of Wisconsin–Madison (US), Janssen (Belgium) (BE), Centre Hospitalier de Luxembourg (LU), University of Cologne (DE), King's College London (GB), University of Oslo (NO), University of Luxembourg (LU), Charles University (CZ), University Hospital Bonn (DE), Stavanger University Hospital (NO), Akershus University Hospital (NO), Sahlgrenska University Hospital (SE), German Center for Neurodegenerative Diseases (DE), Karolinska Institutet (SE), LMU Klinikum (DE), Maastricht University (NL), University of Oxford (GB), Luxembourg Institute of Health (LU), University Hospital of Geneva (CH), Amsterdam Neuroscience (NL), Munich Cluster for Systems Neurology (DE), Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE), Hertie Institute for Clinical Brain Research (DE), Amsterdam University Medical Centers (NL), Luxembourg Centre for Systems Biomedicine (LU), UCL Queen Square Institute of Neurology (GB), Roche Diagnostics International AG (Switzerland) (CH), Fakultní nemocnice Motol a Homolka (CZ), University College London (GB), University of Tübingen (DE), Ludwig-Maximilians-Universität München (DE), Vrije Universiteit Amsterdam (NL), University of Gothenburg (SE), Amsterdam UMC Location Vrije Universiteit Amsterdam (NL), Otto-von-Guericke-Universität Magdeburg (DE)
Dementia and Cognitive Impairment Research
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