Risk of Alzheimer's Disease Biological Misdiagnosis Linked to Cerebrospinal Collection Tubes

Article type: Research Article

Authors: Perret-Liaudet, Armand^{a; b; *} | Pelpel, Mathieu^c | Tholance, Yannick^a | Dumont, Benoit^a | Vanderstichele, Hugo^d | Zorzi, Willy^e | ElMoualij, Benaissa^e | Schraen, Susanna^{b; f} | Moreaud, Olivier^g | Gabelle, Audrey^h | Thouvenot, Eric^h | Thomas-Anterion, Catherineⁱ | Touchon, Jacques^h | Krolak-Salmon, Pierre^a | Kovacs, Gabor G.^j | Coudreuse, Arnaud^k | Quadrio, Isabelle^a | Lehmann, Sylvain^{b; h; *}

Affiliations: [a] Neurobiologie, CMRR, Gériatrie, Hospices Civils de Lyon, Université Lyon 1 – CNRS UMR5292 – INSERM U1028, Lyon, France | [b] Société Française de Biologie Clinique (SFBC), France | [c] Technical and QA Department, Innogenetics, Les Ulis, France | [d] ADx NeuroSciences, Technologiepark, Gent, Belgium | [e] Human Histology-CRPP, University of Liège, Liège, Belgium | [f] CHU de Lille, France; INSERM, U837, France | [g] CMRR, CHU de Grenoble, France | [h] CHU de Montpellier, IRB, INSERM-UM1 1040, INSERM U1061, France | [i] CMRR, Neurologie, CHU de Saint-Etienne, France | [j] Institute of Neurology, Medical University of Vienna, Vienna, Austria | [k] Centre de Transfert de Technologie du Mans, Le Mans, France

Correspondence: [*] Correspondence to: Sylvain Lehmann, Institut de Recherche en Biothérapie, 80 Avenue Augustin Fliche, 34295 Montpellier, France. E-mail: s-lehmann@chu-montpellier.fr and Armand Perret-Liaudet, Service de Neurobiologie, Hospices Civils de Lyon, 69677 Bron, France. E-mail: armand.perret-liaudet@chu-lyon.fr.

Abstract: Tau proteins and amyloid-β (Aβ) peptides are the current recognized cerebrospinal fluid (CSF) biomarkers used as an aid in the diagnosis of Alzheimer's disease (AD). However, there is no consensus on their clinical use due to non-qualified cut-off values, probably related to the observed high pre-analytical and analytical variability. Standardized pre-analytical protocols have therefore been proposed. Importantly, these recommend the use of polypropylene collection/sampling tubes while, to date, no broad comparison of these types of tubes has been conducted. In this study, we first compared, as part of a real clinical workflow, the impact of four different collection tubes on the CSF concentration of Aβ peptides (Aβ42, Aβ40) and total (hTau) and phosphorylated (P-Tau181P) tau proteins measured using routine ELISA kits. We then extended this study to 11 polypropylene tubes used by different clinical laboratories, and investigated their plastic polymer composition using differential scanning calorimetry and Fourier Transformed Infrared spectroscopy. Significant concentration variations linked solely to the use of different types of tubes were observed. This was particularly marked for Aβ peptides, with >50% disparity occurring in less than five minutes. Polymer composition analysis revealed that most polypropylene tubes were in fact copolymers with at least polyethylene. There was no clear correlation between tube composition and pre-analytical behavior. Our results show that the use of polypropylene tubes does not guarantee satisfactory pre-analytical behavior. They also point to collection/sampling tubes being a major pre-analytical source of variability that could impact the significance of AD biological diagnosis.

Keywords: Alzheimer's disease, cerebrospinal fluid, collection tubes, standardization

DOI: 10.3233/JAD-2012-120361

Journal: Journal of Alzheimer's Disease, vol. 31, no. 1, pp. 13-20, 2012