[en] 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Perret-Liaudet, Armand
Pelpel, Mathieu
Tholance, Yannick
Dumont, Benoit
Vanderstichele, Hugo
Zorzi, Willy ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie humaine
Elmoualij, Benaïssa ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie humaine
Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC, Blennow K, Soares H, Simon A, Lewczuk P, Dean R, Siemers E, Potter W, Lee VM, Tro-janowski JQ (2009) Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. Ann Neurol 65, 403-413.
Mattsson N, Zetterberg H, Hansson O, Andreasen N, Parnetti L, Jonsson M, Herukka SK, van der Flier WM, Blankenstein MA, Ewers M, Rich K, Kaiser E, Verbeek M, Tsolaki M, Mulugeta E, Rosén E, Aarsland D, Visser PJ, Schröder J, Marcusson J, de Leon M, Hampel H, Scheltens P, Pirttilä T, Wallin A, Jönhagen ME, Minthon L, Winblad B, Blennow K (2009) CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA 302, 385-393.
Wiltfang J, Esselmann H, Bibl M, Hüll M, Hampel H, Kessler H, Frölich L, Schröder J, Peters O, Jessen F, Luckhaus C, Perneczky R, Jahn H, Fiszer M, Maler JM, Zimmermann R, Bruckmoser R, Kornhuber J, Lewczuk P (2007) Amyloid beta peptide ratio 42/40 but not A beta 42 correlates with phospho-tau in patients with low-and high-CSF A beta 40 load. J Neurochem 101, 1053-1059. (Pubitemid 46683864)
Dubois B, Feldman HH, Jacova C, Cummings JL, Dekosky ST, Barberger-Gateau P, Delacourte A, Frisoni G, Fox NC, Galasko D, Gauthier S, Hampel H, Jicha GA, Meguro K, O'Brien J, Pasquier F, Robert P, Rossor M, Salloway S, Sarazin M, de Souza LC, Stern Y, Visser PJ, Scheltens P (2010) Revising the definition of Alzheimer's disease: A new lexicon. Lancet Neurol 9, 1118-1127.
Andreasen N, Hesse C, Davidsson P, Minthon L, Wallin A, Winblad B, Vanderstichele H, Vanmechelen E, Blennow K (1999) Cerebrospinal fluid beta-amyloid (1-42) in Alzheimer disease: Differences between early-and late-onset Alzheimer disease and stability during the course of disease. Arch Neurol 56, 673-680. (Pubitemid 29266465)
Andreasen N, Blennow K (2005) CSF biomarkers for mild cognitive impairment and early Alzheimer's disease. Clin Neurol Neurosurg 107, 165-173.
Lorenzi M, Donohue M, Paternicò D, Scarpazza C, Ostrow-itzki S, Blin O, Irving E, Frisoni GB, Alzheimer's Disease Neuroimaging Initiative (2010) Enrichment through biomark-ers in clinical trials of Alzheimer's drugs in patients with mild cognitive impairment. Neurobiol Aging 31, 1443-1451.
Teunissen CE, Verwey NA, Kester MI, van Uffelen K, Blankenstein MA (2010) Standardization of assay procedures for analysis of the CSF biomarkers amyloid beta (1-42), tau, and phosphorylated tau in Alzheimer's disease: Report of an international workshop. Int J Alzheimers Dis 2010, pii: 635053.
Mattsson N, Andreasson U, Persson S, Arai H, Batish SD, Bernardini S, Bocchio-Chiavetto L, Blankenstein MA, Car-rillo MC, Chalbot S, Coart E, Chiasserini D, Cutler N, Dahlfors G, Duller S, Fagan AM, Forlenza O, Frisoni GB, Galasko D, Galimberti D, Hampel H, Handberg A, Heneka MT, Herskovits AZ, Herukka SK, Holtzman DM, Humpel C, Hyman BT, Iqbal K, Jucker M, Kaeser SA, Kaiser E, Kapaki E, Kidd D, Klivenyi P, Knudsen CS, Kummer MP, Lui J, Lladó A, Lewczuk P, Li QX, Martins R, Masters C, McAuliffe J, Mercken M, Moghekar A, Molinuevo JL, Mon-tine TJ, Nowatzke W, rsquo O, Brien R, Otto M, Paraskevas GP, Parnetti L, Petersen RC, Prvulovic D, de Reus HP, Riss-man RA, Scarpini E, Stefani A, Soininen H, Schröder J, Shaw LM, Skinningsrud A, Skrogstad B, Spreer A, Talib L, Teunis-sen C, Trojanowski JQ, Tumani H, Umek RM, Van Broeck B, Vanderstichele H, Vecsei L, Verbeek MM, Windisch M, Zhang J, Zetterberg H, Blennow K (2011) The Alzheimer's association external quality control program for cerebrospinal fluid biomarkers. Alzheimers Dement 7, 386-395.
Bjerke M, Portelius E, Minthon L, Wallin A, Anckarsäter H, Anckarsäter R, Andreasen N, Zetterberg H, Andreasson U, Blennow K (2010) Confounding factors influencing amyloid beta concentration in cerebrospinal fluid. Int J Alzheimers Dis 2010, pii: 986310.
Lewczuk P, Beck G, Esselmann H, Bruckmoser R, Zimmer-mann R, Fiszer M, Bibl M, Maler JM, Kornhuber J, Wiltfang J (2006) Effect of sample collection tubes on cerebrospinal fluid concentrations of tau proteins and amyloid betapeptides. Clin Chem 52, 332-334. (Pubitemid 43185505)
Andreasen N, Minthon L, Davidsson P, Vanmechelen E, Van-derstichele H, Winblad B, Blennow K (2001) Evaluation of CSF-tau and csf-abeta42 as diagnostic markers for Alzheimer disease in clinical practice. Arch Neurol 58, 373-379. (Pubitemid 32217453)
Slemmon JR, Meredith J, Guss V, Andreasson U, Andreasen N, Zetterberg H, Blennow K (2011) Measurement of Abeta1-42 in cerebrospinal fluid is influenced by matrix effects. J Neurochem 120, 325-333.
Pica-Mendez AM, Tanen M, Dallob A, Tanaka W, Laterza OF (2010) Nonspecific binding of Abeta42 to polypropylene tubes and the effect of tween-20. Clin Chim Acta 411, 33.
Perret-Liaudet A, Pelpel M, Tholance Y, Dumont B, Van-derstichele H, Zorzi W, Elmoualij B, Schraen S, Moreaud O, Gabelle A, Thouvenot E, Thomas-Anterion C, Touchon J, Krolak-Salmon P, Kovacs GG, Coudreuse A, Quadrio I, Lehmann S (2012) Cerebrospinal fluid collection tubes: A critical issue for Alzheimer disease diagnosis. Clin Chem 58, 787-789.
Sweileh BA, Al-Hiari YM, Kailani MH, Mohammad HA (2010) Synthesis and characterization of polycarbonates by melt phase interchange reactions of alkylene and arylene diacetates with alkylene and arylene diphenyl dicarbonates. Molecules 15, 3661-3682.
Nakanishi K, Sakiyama T, Imamura K (2001) On the adsorption of proteins on solid surfaces, a common but very complicated phenomenon. J Biosci Bioeng 91, 233-244. (Pubitemid 32324614)
Gabelle A, Roche S, Gény C, Bennys K, Labauge P, Tholance Y, Quadrio I, Tiers L, Gor B, Boulanghien J, Chaulet C, Vighetto A, Croisile B, Krolak-Salmon P, Perret-Liaudet A, Touchon J, Lehmann S (2011) Decreased sAβPPβ, Aβ38 and Aβ40 cerebrospinal fluid levels in frontotemporal dementia. J Alzheimers Dis 26, 553-563.
Duncan M, Lee J, Warchol M (1995) Influence of surfactants upon protein/peptide adsorption to glass and polypropylene. Int J Pharm 120, 179-188.
Poncin-Epaillard F, Mille C, Debarnot D, Zorzi W, Moualij BE, Coudreuse A, Legeay G, Quadrio I, Perret-Liaudet A (2011) Study of the adhesion of neurodegenerative proteins on plasma-modified and coated polypropylene surfaces. J Biomater Sci Polym Ed 2011 Sep 28. Epub ahead of print.
Zanini S, Riccardi C, Grimoldi E, Colombo C, Villa AM, Natalello A, Gatti-Lafranconi P, Lotti M, Doglia SM (2010) Plasma-induced graft-polymerization of polyethylene glycol acrylate on polypropylene films: Chemical characterization and evaluation of the protein adsorption. J Colloid Interface Sci 341, 53-58.