Abstract
Adsorption of CSF Aβ1–42 during pre-analytical processing is suggested as an important confounder in testing. The aim of the present study was to assess the effect of polypropylene transfer plates (PTP) in the INNOTEST Aβ1–42 IVD-ELISA assay on Aβ1–42 levels. CSF samples from 26 individuals with subjective cognitive impairment (SCI) and 25 patients with suspected neurodegenerative disorders were tested using four different lots of kits. Aβ1–42 levels in all samples that were loaded onto the PTP were significantly lower than the levels in the same samples that were analyzed without prior loading onto the PTP. We found that the PTP may adsorb Aβ1–42 in the range 7 to 69%. The diagnosis in 20% of patients and amyloid burden assessment in 23% of SCI patients had to be modified post hoc due to initial erroneously low amyloid levels. Using a PTP prior to loading the samples onto the INNOTEST Aβ1–42 test plate may result in erroneously low Aβ1–42 levels.
References
Alzheimer's Association (2012) 2012 Alzheimer’s disease facts and figures. Alzheimers Dement 8(2):131–168. https://doi.org/10.1016/j.jalz.2012.02.001
Cullen VC, Fredenburg RA, Evans C, Conliffe PR, Solomon ME (2012) Development and advanced validation of an optimized method for the quantitation of Abeta42 in human cerebrospinal fluid. AAPS J 14(3):510–518. https://doi.org/10.1208/s12248-012-9360-7
del Campo M, Mollenhauer B, Bertolotto A, Engelborghs S, Hampel H, Simonsen AH, Kapaki E, Kruse N, Le Bastard N, Lehmann S, Molinuevo JL, Parnetti L, Perret-Liaudet A, Saez-Valero J, Saka E, Urbani A, Vanmechelen E, Verbeek M, Visser PJ, Teunissen C (2012) Recommendations to standardize preanalytical confounding factors in Alzheimer's and Parkinson's disease cerebrospinal fluid biomarkers: an update. Biomark Med 6(4):419–430. https://doi.org/10.2217/bmm.12.46
Duits FH, Teunissen CE, Bouwman FH, Visser PJ, Mattsson N, Zetterberg H, Blennow K, Hansson O, Minthon L, Andreasen N, Marcusson J, Wallin A, Rikkert MO, Tsolaki M, Parnetti L, Herukka SK, Hampel H, De Leon MJ, Schroder J, Aarsland D, Blankenstein MA, Scheltens P, van der Flier WM (2014) The cerebrospinal fluid “Alzheimer profile”: easily said, but what does it mean? Alzheimers Dement 10(6):713–723 e712. https://doi.org/10.1016/j.jalz.2013.12.023
Fourier A, Portelius E, Zetterberg H, Blennow K, Quadrio I, Perret-Liaudet A (2015) Pre-analytical and analytical factors influencing Alzheimer's disease cerebrospinal fluid biomarker variability. Clin Chim Acta 449:9–15. https://doi.org/10.1016/j.cca.2015.05.024
Gezen-Ak D, Yilmazer S, Dursun E (2014) Why vitamin D in Alzheimer's disease? The hypothesis. J Alzheimers Dis 40(2):257–269. https://doi.org/10.3233/JAD-131970
Illan-Gala I, Vilaplana E, Pegueroles J, Montal V, Alcolea D, Blesa R, Lleo A, Fortea J, Alzheimer's Disease Neuroimaging I (2017) The pitfalls of biomarker-based classification schemes. Alzheimers Dement 13(9):1072–1074. https://doi.org/10.1016/j.jalz.2017.06.002
Perret-Liaudet A, Pelpel M, Tholance Y, Dumont B, Vanderstichele 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) Risk of Alzheimer's disease biological misdiagnosis linked to cerebrospinal collection tubes. J Alzheimers Dis 31(1):13–20. https://doi.org/10.3233/JAD-2012-120361
Schindler SE, Sutphen CL, Teunissen C, McCue LM, Morris JC, Holtzman DM, Mulder SD, Scheltens P, Xiong C, Fagan AM (2018) Upward drift in cerebrospinal fluid amyloid beta 42 assay values for more than 10 years. Alzheimers Dement 14(1):62–70. https://doi.org/10.1016/j.jalz.2017.06.2264
Stohr J, Watts JC, Mensinger ZL, Oehler A, Grillo SK, DeArmond SJ, Prusiner SB, Giles K (2012) Purified and synthetic Alzheimer's amyloid beta (Abeta) prions. Proc Natl Acad Sci U S A 109(27):11025–11030. https://doi.org/10.1073/pnas.1206555109
Tapiola T, Alafuzoff I, Herukka SK, Parkkinen L, Hartikainen P, Soininen H, Pirttila T (2009) Cerebrospinal fluid {beta}-amyloid 42 and tau proteins as biomarkers of Alzheimer-type pathologic changes in the brain. Arch Neurol 66(3):382–389. https://doi.org/10.1001/archneurol.2008.596
Vanderstichele H, Demeyer L, Janelidze S, Coart E, Stoops E, Mauroo K, Herbst V, Francois C, Hansson O (2017) Recommendations for cerebrospinal fluid collection for the analysis by ELISA of neurogranin trunc P75, alpha-synuclein, and total tau in combination with Abeta(1-42)/Abeta(1-40). Alzheimers Res Ther 9(1):40. https://doi.org/10.1186/s13195-017-0265-7
Vrlinic T, Debarnot D, Legeay G, Coudreuse A, El Moualij B, Zorzi W, Perret-Liaudet A, Quadrio I, Mozetic M, Poncin-Epaillard F (2012) Are the interactions between recombinant prion proteins and polymeric surfaces related to the hydrophilic/hydrophobic balance? Macromol Biosci 12(6):830–839. https://doi.org/10.1002/mabi.201100454
Willemse E, van Uffelen K, Brix B, Engelborghs S, Vanderstichele H, Teunissen C (2017) How to handle adsorption of cerebrospinal fluid amyloid beta (1-42) in laboratory practice? Identifying problematic handlings and resolving the issue by use of the Abeta42/Abeta40 ratio. Alzheimers Dement 13(8):885–892. https://doi.org/10.1016/j.jalz.2017.01.010
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The English of the manuscript has been edited by EDANZ Language Editing Service with the reference number 17590.
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The present work was supported by the Scientific and Technological Research Council of Turkey-TUBITAK (Project No. 112S361) and by the Research Fund of Istanbul University (Project no: 27781).
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Erdinç Dursun: study concept and design, analysis and interpretation of data, study supervision, drafting and revision of manuscript for intellectual content
Merve Alaylıoğlu: study concept and design, acquisition and analysis of data
Başar Bilgiç: acquisition of data, revision of manuscript for intellectual content
Haşmet Hanağası: acquisition of data, revision of manuscript for intellectual content
Hakan Gürvit: acquisition of data, revision of manuscript for intellectual content
Murat Emre: acquisition of data, revision of manuscript for intellectual content
Duygu Gezen-Ak: study concept and design, acquisition, analysis, and interpretation of data, study supervision, drafting and revision of manuscript for intellectual content
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Dursun, E., Alaylıoğlu, M., Bilgiç, B. et al. Amyloid Beta Adsorption Problem with Transfer Plates in Amyloid Beta 1–42 IVD Kits. J Mol Neurosci 67, 534–539 (2019). https://doi.org/10.1007/s12031-019-1261-0
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DOI: https://doi.org/10.1007/s12031-019-1261-0