title: Risk of Alzheimer's disease biological misdiagnosis linked to cerebrospinal collection tubes.
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.
authors.affiliation: Neurobiologie, CMRR, Gériatrie, Hospices Civils de Lyon, Université Lyon 1-CNRS UMR5292-INSERM U1028, Lyon, France. armand.perret-liaudet@chu-lyon.fr
authors.forename: Armand
authors.initials: A
authors.lastname: Perret-Liaudet
authors.forename: Mathieu
authors.initials: M
authors.lastname: Pelpel
authors.forename: Yannick
authors.initials: Y
authors.lastname: Tholance
authors.forename: Benoit
authors.initials: B
authors.lastname: Dumont
authors.forename: Hugo
authors.initials: H
authors.lastname: Vanderstichele
authors.forename: Willy
authors.initials: W
authors.lastname: Zorzi
authors.forename: Benaissa
authors.initials: B
authors.lastname: Elmoualij
authors.forename: Susanna
authors.initials: S
authors.lastname: Schraen
authors.forename: Olivier
authors.initials: O
authors.lastname: Moreaud
authors.forename: Audrey
authors.initials: A
authors.lastname: Gabelle
authors.forename: Eric
authors.initials: E
authors.lastname: Thouvenot
authors.forename: Catherine
authors.initials: C
authors.lastname: Thomas-Anterion
authors.forename: Jacques
authors.initials: J
authors.lastname: Touchon
authors.forename: Pierre
authors.initials: P
authors.lastname: Krolak-Salmon
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Kovacs
authors.forename: Arnaud
authors.initials: A
authors.lastname: Coudreuse
authors.forename: Isabelle
authors.initials: I
authors.lastname: Quadrio
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lehmann
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D003951:Diagnostic Errors; D004797:Enzyme-Linked Immunosorbent Assay; D005583:Fourier Analysis; D006801:Humans; D010766:Phosphorylation; D012306:Risk; D013055:Spectrophotometry, Infrared; D018709:Statistics, Nonparametric; D013997:Time Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins