Comparison of different matrices as potential quality control samples for neurochemical dementia diagnostics

N. Lelental, S. Brandner, O. Kofanova, K. Blennow, H. Zetterberg, U. Andreasson, S. Engelborghs, B. Mroczko, T. Gabryelewicz, C. Teunissen, B. Mollenhauer, L. Parnetti, D. Chiasserini, J.L. Molinuevo, A. Perret-Liaudet, M.M. Verbeek, N. Andreasen, F. Brosseron, J.M. Bahl, S.K. Herukka, L. Hausner, L. Frolich, A. Labonte, J. Poirier, A.M. Miller, N. Zilka, B. Kovacech, A. Urbani, S. Suardi, C. Oliveira, I. Baldeiras, B. Dubois, U. Rot, S. Lehmann, A. Skinningsrud, F. Betsou, J. Wiltfang, O. Gkatzima, B. Winblad, M. Buchfelder, J. Kornhuber, P. Lewczuk.

Journal of Alzheimer’s disease, Volume 52, Article number: 51-64 (2016), doi:10.3233/JAD-150883


Assay-vendor independent quality control (QC) samples for neurochemical dementia diagnostics (NDD) biomarkers are so far commercially unavailable. This  requires that NDD laboratories prepare their own QC samples, for example by pooling leftover cerebrospinal fluid (CSF) samples.


To prepare and test alternative matrices for QC samples that could facilitate intra- and inter-laboratory QC of the NDD biomarkers.


Three matrices were validated in this study: (A) human pooled CSF, (B) A peptides spiked into human prediluted plasma, and (C) A peptides spiked into solution of bovine serum albumin in phosphate-buffered saline. All matrices were tested also after supplementation with an antibacterial agent (sodium azide). We analyzed short- and long-term stability of the biomarkers with ELISA and chemiluminescence (Fujirebio Europe, MSD, IBL International), and performed an inter-laboratory variability study.


NDD biomarkers turned out to be stable in almost all samples stored at the tested conditions for up to 14 days as well as in samples stored deep-frozen (at –80◦C) for up to one year. Sodium azide did not influence biomarker stability. Inter-center variability of the samples sent at room temperature (pooled CSF, freeze-dried CSF, and four artificial matrices) was comparable to the results obtained on deep-frozen samples in other large-scale projects.


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.