No abstract

Biobanks are important resources for biomarker discovery and assay development. Biomarkers for Alzheimer’s and Parkinson’s disease (BIOMARKAPD) is a European multicenter study, funded by the EU Joint Programme-Neurodegenerative Disease Research, which aims to improve the clinical use of body fluid markers for the diagnosis and prognosis of Alzheimer’s disease (AD) and Parkinson’s disease (PD). The objective was to standardize the assessment of existing assays and to validate novel fluid biomarkers for AD and PD. To support the validation of novel biomarkers and assays, a central and a virtual biobank for body fluids and associated data from subjects with neurodegenerative diseases have been established. In the central biobank, cerebrospinal fluid (CSF) and blood samples were collected according to the BIOMARKAPD standardized pre-analytical procedures and stored at Integrated BioBank of Luxembourg. The virtual biobank provides an overview of available CSF, plasma, serum, and DNA samples at each site. Currently, at the central biobank of BIOMARKAPD samples are available from over 400 subjects with normal cognition, mild cognitive impairment (MCI), AD, frontotemporal dementia (FTD), vascular dementia, multiple system atrophy, progressive supranuclear palsy, PD, PD with dementia, and dementia with Lewy bodies. The virtual biobank contains information on over 8,600 subjects with varying diagnoses from 21 local biobanks. A website has been launched to enable sample requests from the central biobank and virtual biobank.

Our results suggest that it is possible to replace self-made, CSF-based QC samples with large-scale volumes of QC materials prepared with artificial peptides and matrices. This would greatly facilitate intra- and inter-laboratory QC schedules for NDD measurements.

Aim: Neurofilament light (NfL) chain, a putative cerebrospinal fluid biomarker, can support neurodegenerative disease diagnosis and indicate disease severity and prognosis. Universal validation protocols when used to measure biomarkers can reduce pre and analytical laboratory variation, thus increasing end-user confidence in the consistency of validation data across sites. Methodology: Here, a commercially available NfL ELISA (UmanDiagnostics, Umeå, Sweden) was validated in a multicentered setting using comprehensive newly developed standard operating procedures. Results: The data showed good assay sensitivity and intra and interassay precision. Interlaboratory precision was, however, suboptimal. Conclusion: The UmanDiagnostics assay is suitable for the quantification of NfL in human cerebrospinal fluid. However, sources of interlaboratory variation in the data require further investigation.

Variations in attitude and practice relating to CSF biomarkers, widely recognised as barriers to their clinical acceptance, remain evident within and between countries across Europe, even in expert centres. These shortcomings must be addressed by developing consensus guidelines on CSF-related methodologies and their clinical application, to further their use for the diagnostic evaluation of dementia.