Comparison of Different Matrices as Potential Quality Control Samples for Neurochemical Dementia Diagnostics

Article type: Research Article

Authors: Lelental, Natalia^a | Brandner, Sebastian^b | Kofanova, Olga^c | Blennow, Kaj^d | Zetterberg, Henrik^{d; e} | Andreasson, Ulf^d | Engelborghs, Sebastiaan^f | Mroczko, Barbara^g | Gabryelewicz, Tomasz^h | Teunissen, Charlotteⁱ | Mollenhauer, Brit^j | Parnetti, Lucilla^k | Chiasserini, Davide^k | Molinuevo, Jose Luis^l | Perret-Liaudet, Armand^m | Verbeek, Marcel M.ⁿ | Andreasen, Niels^o | Brosseron, Frederic^p | Bahl, Justyna M.C.^q | Herukka, Sanna-Kaisa^r | Hausner, Lucrezia^s | Frölich, Lutz^s | Labonte, Anne^t | Poirier, Judes^t | Miller, Anne-Marie^u | Zilka, Norbert^v | Kovacech, Branislav^v | Urbani, Andrea^w | Suardi, Silvia^x | Oliveira, Catarina^y | Baldeiras, Ines^y | Dubois, Bruno^z | Rot, Uros^aa | Lehmann, Sylvain^ab | Skinningsrud, Anders^ac | Betsou, Fay^c | Wiltfang, Jens^ad | Gkatzima, Olymbia^ae | Winblad, Bengt^af | Buchfelder, Michael^b | Kornhuber, Johannes^a | Lewczuk, Piotr^{a; g; *}

Affiliations: [a] Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany | [b] Department of Neurosurgery, Universitätsklinikum Erlangen, and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany | [c] Integrated BioBank of Luxembourg, Luxembourg | [d] Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden | [e] Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK | [f] Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, and Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium | [g] Department of Neurodegeneration Diagnostics, Medical University of Białystok, and Department of Biochemical Diagnostics, University Hospital of Białystok, Białystok, Poland | [h] Department of Neurodegenerative Disorders, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland | [i] Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands | [j] Paracelsus-Elena-Klinik, Kassel and University Medical Center Göttingen, Institute of Neuropathology and Department of Neurosurgery, Germany | [k] Laboratory of Clinical Neurochemistry, Department of Medicine, Section of Neurology, University of Perugia, Perugia, Italy | [l] Alzheimer’s Disease and Other Cognitive Disorders Unit, Hospital Clinic, IDIBAPS, Barcelona, Spain | [m] Hospices Civils de Lyon, Groupement Hospitalier Est, Biochemistry Department, Neurochemistry unit; Lyon University, Lyon Neuroscience Research Center, INSERM U1028, CNRS UMR 5292, BioRaN Team, France | [n] Department of Neurology, Donders Institute for Brain, Cognition and Behaviour Neurochemistry Lab – Translational Metabolic Laboratory, Dept. of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands | [o] Geriatriska kliniken, Karolinska Universitetssjukhuset, Huddinge, Stockholm, Sweden | [p] German Center for Neurodegenerative Diseases (DZNE) e.V., Clinical Neuroscience and Biomarkers, and University Clinic Bonn, Clinic and Polyclinic for Neurology, Bonn, Germany | [q] Department of Autoimmunology and Biomarkers, Statens Serum Institut, Copenhagen, Denmark | [r] Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland | [s] Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany | [t] Centre for Studies in Alzheimer’s disease Prevention, Douglas Mental Health University Institute, LaSalle, Verdun, PQ, Canada | [u] Medical Gerontology, School of Medicine, Trinity College Dublin, Dublin, Ireland | [v] Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia | [w] IRCCS-Santa Lucia Foundation, Rome, and Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata”, Rome, Italy | [x] Neuropathology Laboratory, Neurological Institute C. Besta, Milan, Italy | [y] Neurochemistry Laboratory, Faculty of Medicine, CHUC– Coimbra University Hospital, CNC, CNC. IBILI-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal | [z] Centre des Maladies Cognitives et Comportementales (IM2A), Institut du Cerveau et de la Moelle épinière (ICM), UMR-S975, Université Pierre et Marie Curie- Paris, AP-HP, Hôpital de la Salpêtrière, Paris, France | [aa] Laboratory for CSF diagnostics, Department of Neurology, University Medical Centre, Ljubljana, Slovenia | [ab] Laboratoire de Biochimie et de Protéomique Clinique - Institut de Médecine Régénérative et Biothérapies, Centre Hospitalier Universitaire de Montpellier, Montpellier, France | [ac] Multidiciplinary Laboratory Medicine and Medical Biochemistry, Division of Diagnostics and Technology, Akershus University Hospital, Lørenskog, Norway | [ad] Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August University, Göttingen, Germany | [ae] 3rd Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece | [af] Karolinska Institutet, Dept NVS, Center for Alzheimer Research, Division of Neurogeriatrics, Huddinge, Sweden

Correspondence: [*] Correspondence to: Prof. Dr. med. Piotr Lewczuk, Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics, Department of Psychiatry and Psychotherapy, Schwabachanlage 6, 91054 Erlangen, Germany. Tel.: +49 9131 85 34324; Fax: +49 9131 85 34238; E-mail: Piotr.Lewczuk@uk-erlangen.de.

Abstract: Background: 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. Objective: To prepare and test alternative matrices for QC samples that could facilitate intra- and inter-laboratory QC of the NDD biomarkers. Methods: Three matrices were validated in this study: (A) human pooled CSF, (B) Aβ peptides spiked into human prediluted plasma, and (C) Aβ 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. Results: 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. Conclusion: 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.

Keywords: Alzheimer’s disease, amyloid-β, biomarkers, cerebrospinal fluid, laboratory diagnostics, quality control, tau

DOI: 10.3233/JAD-150883

Journal: Journal of Alzheimer's Disease, vol. 52, no. 1, pp. 51-64, 2016