Preanalytical sample handling recommendations for Alzheimer's disease plasma biomarkers
Małgorzata Rózga, Tobias Bittner, Richard Batrla, Johann Karl, Małgorzata Rózga, Tobias Bittner, Richard Batrla, Johann Karl
Abstract
Introduction: We examined the influence of common preanalytical factors on the measurement of Alzheimer's disease-specific biomarkers in human plasma.
Methods: Amyloid β peptides (Aβ[1-40], Aβ[1-42]) and total Tau plasma concentrations were quantified using fully automated Roche Elecsys assays.
Results: Aβ(1-40), Aβ(1-42), and total Tau plasma concentrations were not affected by up to three freeze/thaw cycles, up to five tube transfers, the collection tube material, or the size; circadian rhythm had a minor effect. All three biomarkers were influenced by the anticoagulant used, particularly total Tau. Aβ concentrations began decreasing 1 hour after blood draw/before centrifugation and decreased by up to 5% and 10% at 2 and 6 hours, respectively. For separated plasma, time to measurement influenced Aβ levels by up to 7% after 6 hours and 10% after 24 hours.
Discussion: Our findings provide guidance for standardizing blood sample collection, handling, and storage to ensure reliable analysis of Alzheimer's disease plasma biomarkers in routine practice and clinical trials.
Keywords: AD; Alzheimer's disease; Alzheimer's disease-specific biomarkers; Amyloid; Biomarkers; Elecsys immunoassay; Fully automated; Plasma; Preanalytics; Sample handling; Tau.
Figures
References
- Waldemar G., Phung K.T., Burns A., Georges J., Hansen F.R., Iliffe S. Access to diagnostic evaluation and treatment for dementia in Europe. Int J Geriatr Psychiatry. 2007;22:47–54.
- Beach T.G., Monsell S.E., Phillips L.E., Kukull W. Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease Centers, 2005-2010. J Neuropathol Exp Neurol. 2012;71:266–273.
- Sabbagh M.N., Lue L.F., Fayard D., Shi J. Increasing precision of clinical diagnosis of Alzheimer's disease using a combined algorithm incorporating clinical and novel biomarker data. Neurol Ther. 2017;6:83–95.
- Simonsen A.H., Herukka S.K., Andreasen N., Baldeiras I., Bjerke M., Blennow K. Recommendations for CSF AD biomarkers in the diagnostic evaluation of dementia. Alzheimers Dement. 2017;13:274–284.
- Blennow K., Zetterberg H. Cerebrospinal fluid biomarkers for Alzheimer's disease. J Alzheimers Dis. 2009;18:413–417.
- Holtzman D.M. CSF biomarkers for Alzheimer's disease: current utility and potential future use. Neurobiol Aging. 2011;32:S4–S9.
- Engelborghs S., De Vreese K., Van de Casteele T., Vanderstichele H., Van Everbroeck B., Cras P. Diagnostic performance of a CSF-biomarker panel in autopsy-confirmed dementia. Neurobiol Aging. 2008;29:1143–1159.
- McKhann G.M., Knopman D.S., Chertkow H., Hyman B.T., Jack C.R., Jr., Kawas C.H. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7:263–269.
- Dubois B., Feldman H.H., Jacova C., Hampel H., Molinuevo J.L., Blennow K. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria. Lancet Neurol. 2014;13:614–629.
- Jack C.R., Jr., Bennett D.A., Blennow K., Carrillo M.C., Dunn B., Haeberlein S.B. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018;14:535–562.
- Hampel H., O'Bryant S.E., Molinuevo J.L., Zetterberg H., Masters C.L., Lista S. Blood-based biomarkers for Alzheimer disease: mapping the road to the clinic. Nat Rev Neurol. 2018;14:639–652.
- O'Bryant S.E., Mielke M.M., Rissman R.A., Lista S., Vanderstichele H., Zetterberg H. Blood-based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic. Alzheimers Dement. 2017;13:45–58.
- Hansson O., Mikulskis A., Fagan A.M., Teunissen C., Zetterberg H., Vanderstichele H. The impact of preanalytical variables on measuring cerebrospinal fluid biomarkers for Alzheimer's disease diagnosis: A review. Alzheimers Dement. 2018;14:1313–1333.
- Ovod V., Ramsey K.N., Mawuenyega K.G., Bollinger J.G., Hicks T., Schneider T. Amyloid β concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis. Alzheimers Dement. 2017;13:841–849.
- Nakamura A., Kaneko N., Villemagne V.L., Kato T., Doecke J., Doré V. High performance plasma amyloid-β biomarkers for Alzheimer's disease. Nature. 2018;554:249–254.
- Verberk I.M.W., Slot R.E., Verfaillie S.C.J., Heijst H., Prins N.D., van Berckel B.N.M. Plasma amyloid as prescreener for the earliest Alzheimer pathological changes. Ann Neurol. 2018;84:648–658.
- Teunissen C.E., Chiu M.J., Yang C.C., Yang S.Y., Scheltens P., Zetterberg H. Plasma amyloid-β (Aβ42) correlates with cerebrospinal fluid Aβ42 in Alzheimer's disease. J Alzheimers Dis. 2018;62:1857–1863.
- Bittner T., Zetterberg H., Teunissen C.E., Ostlund R.E., Jr., Militello M., Andreasson U. Technical performance of a novel, fully automated electrochemiluminescence immunoassay for the quantitation of β-amyloid (1-42) in human cerebrospinal fluid. Alzheimers Dement. 2016;12:517–526.
- England J.M., Rowan R.M., van Assendelft O.W., Bull B.S., Coulter W., Fujimoto K. Recommendations of the International Council for Standardization in Haematology for Ethylenediaminetetraacetic Acid Anticoagulation of Blood for Blood Cell Counting and Sizing. International Council for Standardization in Haematology: Expert Panel on Cytometry. Am J Clin Pathol. 1993;100:371–372.
- Lippi G., Guidi G.C., Mattiuzzi C., Plebani M. Preanalytical variability: the dark side of the moon in laboratory testing. Clin Chem Lab Med. 2006;44:358–365.
- Bjerke M., Portelius E., Minthon L., Wallin A., Anckarsäter H., Anckarsäter R. Confounding factors influencing amyloid beta concentration in cerebrospinal fluid. Int J Alzheimers Dis. 2010;2010 pii:986310.
- Fourier A., Portelius E., Zetterberg H., Blennow K., Quadrio I., Perret-Liaudet A. Pre-analytical and analytical factors influencing Alzheimer's disease cerebrospinal fluid biomarker variability. Clin Chim Acta. 2015;449:9–15.
- Vanderstichele H., Bibl M., Engelborghs S., Le Bastard N., Lewczuk P., Molinuevo J.L. Standardization of preanalytical aspects of cerebrospinal fluid biomarker testing for Alzheimer's disease diagnosis: a consensus paper from the Alzheimer's Biomarkers Standardization Initiative. Alzheimers Dement. 2012;8:65–73.
- Rivera-Coll A., Fuentes-Arderiu X., Díez-Noguera A. Circadian rhythms of serum concentrations of 12 enzymes of clinical interest. Chronobiol Int. 1993;10:190–200.
- Fournier S., Iten L., Marques-Vidal P., Boulat O., Bardy D., Beggah A. Circadian rhythm of blood cardiac troponin T concentration. Clin Res Cardiol. 2017;106:1026–1032.
- Lachno D.R., Vanderstichele H., De Groote G., Kostanjevecki V., De Meyer G., Siemers E.R. The influence of matrix type, diurnal rhythm and sample collection and processing on the measurement of plasma beta-amyloid isoforms using the INNO-BIA plasma Abeta forms multiplex assay. J Nutr Health Aging. 2009;13:220–225.
- Lewczuk P., Beck G., Esselmann H., Bruckmoser R., Zimmermann R., Fiszer M. Effect of sample collection tubes on cerebrospinal fluid concentrations of tau proteins and amyloid beta peptides. Clin Chem. 2006;52:332–334.
- Pica-Mendez A.M., Tanen M., Dallob A., Tanaka W., Laterza O.F. Nonspecific binding of Aβ42 to polypropylene tubes and the effect of Tween-20. Clin Chim Acta. 2010;411:1833.
- Perret-Liaudet A., Pelpel M., Tholance Y., Dumont B., Vanderstichele H., Zorzi W. Risk of Alzheimer's disease biological misdiagnosis linked to cerebrospinal collection tubes. J Alzheimers Dis. 2012;31:13–20.
- Clark S., Youngman L.D., Palmer A., Parish S., Peto R., Collins R. Stability of plasma analytes after delayed separation of whole blood: implications for epidemiological studies. Int J Epidemiol. 2003;32:125–130.
- Böttger R., Hoffmann R., Knappe D. Differential stability of therapeutic peptides with different proteolytic cleavage sites in blood, plasma and serum. PLoS One. 2017;12:e0178943.
- Dufresne J., Florentinus-Mefailoski A., Ajambo J., Ferwa A., Bowden P., Marshall J. The proteins cleaved by endogenous tryptic proteases in normal EDTA plasma by C18 collection of peptides for liquid chromatography micro electrospray ionization and tandem mass spectrometry. Clin Proteomics. 2017;14:39.
- Kaisar M., van Dullemen L.F.A., Thézénas M.L., Zeeshan Akhtar M., Huang H., Rendel S. Plasma degradome affected by variable storage of human blood. Clin Proteomics. 2016;13:26.
- Finder V.H., Glockshuber R. Amyloid-beta aggregation. Neurodegener Dis. 2007;4:13–27.
- Tiiman A., Krishtal J., Palumaa P., Tõugu V. In vitro fibrillization of Alzheimer's amyloid-β peptide (1-42) AIP Adv. 2015;5:092401.
- Lachno D.R., Emerson J.K., Vanderstichele H., Gonzales C., Martényi F., Konrad R.J. Validation of a multiplex assay for simultaneous quantification of amyloid-β peptide species in human plasma with utility for measurements in studies of Alzheimer's disease therapeutics. J Alzheimers Dis. 2012;32:905–918.
- Keshavan A., Heslegrave A., Zetterberg H., Schott J.M. Stability of blood-based biomarkers of Alzheimer's disease over multiple freeze-thaw cycles. Alzheimers Dement (Amst) 2018;10:448–451.
Source: PubMed