What are the complement datasets?

The complement datasets were generated through the second biomarker case study, released by the European Platform for Neurodegenerative Diseases (EPND).

The complement system is part of the innate immune response, and there is growing interest in its role in neurodegenerative disease. The case study set out to assess the feasibility, analytical validity and clinical validity of the complement assays currently available, comparing measurements across several platforms in the same participants. In doing so, it also tested the EPND platform itself, including the processes for transferring samples between academic and industry partners.

The complement case study draws on the same samples and the same participating centres as the ATN biomarker dataset, from EPND's first biomarker case study. Researchers can therefore use the two datasets together, studying complement measures as well as the ATN biomarker profiles for the same individuals.

What does the dataset contain?

The complement biomarker case study generated measures of complement proteins across four technical platforms, yielding four separate datasets

CSF Merck Milliplex complement panel data are available for 325 participants, centrally measured at DZNE. CSF SomaScan 7k data are available for 325 participants, centrally measured at SomaLogic. CSF Olink Explore 3072 data are available for 328 participants, covering all eight panels (Cardiometabolic, Cardiometabolic II, Inflammation, Inflammation II, Neurology, Neurology II, Oncology and Oncology II), centrally measured at Sanofi. Plasma and serum complement data were generated using SVAR assays. For 341 participants, plasma measures of terminal complement complex, factor P and C4d are available. For a subset of 30 participants, serum measures of classical pathway, MBL pathway and alternative pathway activity are also available.

The dataset also includes CSF and plasma Aß42, Aß40, p-tau181, NfL and CSF α-synuclein, measured centrally using Roche's NeuroToolKit for all participants. These are linked to data on demographics, clinical factors, lifestyle, rating scales, cognition, samples, genetics and imaging.

Which cohorts were involved in the complement case study?

The case study was led by Pieter Jelle Visser, Professor in Molecular Epidemiology of Alzheimer's Disease at the University of Maastricht. It draws on a mixed cohort of 350 people with Alzheimer's disease, Parkinson's disease and dementia with Lewy bodies, together with controls.

As with the ATN case study, the samples were contributed by seven European studies, comprising ten cohorts across six countries (Germany, Czechia, Norway, Switzerland, Luxembourg and the Netherlands), at the following institutions: Akershus University Hospital (DDI cohort), Deutsches Zentrum für Neurodegenerative Erkrankungen (DANCER, DELCODE, DESCRIBE and MIGAP cohorts), Motol University Hospital (CBAS cohort), Stavanger University Hospital (NOR-DLB cohort), University of Geneva (COSCODE/gMAD cohort), University of Luxembourg (LuxPark cohort) and Amsterdam UMC (ADC cohort).

Information on all these studies and cohorts can be found on the EPND Hub.

How can researchers access and analyse the complement datasets?

The complement datasets are accessible through the EPND Hub, a secure platform designed to facilitate data and biosample discovery, access and analysis. Through EPND's interoperability with the Alzheimer's Disease Data Initiative's AD Workbench, registered users can analyse data securely in personal, cloud-based workspaces using a unified login.

What is the EPND Hub and how can it support collaborative research?

The EPND Hub provides researchers with tools to search, filter and visualise neurodegenerative disease datasets and biosamples, including the complement dataset. It supports secure collaboration, federated data access and advanced analysis, through its interoperability with the AD Data Initiative's AD Workbench. Its ELSI Support Desk helps researchers to navigate ethical and legal considerations whilst collaborating via the Hub, providing guidance on data protection, research ethics and contractual arrangements.

Click here to access the complement dataset listings on the EPND Hub.