TY - JOUR
T1 - The impact of preanalytical variables on measuring cerebrospinal fluid biomarkers for Alzheimer's disease diagnosis
T2 - A review
AU - Hansson, Oskar
AU - Mikulskis, Alvydas
AU - Fagan, Anne M.
AU - Teunissen, Charlotte
AU - Zetterberg, Henrik
AU - Vanderstichele, Hugo
AU - Molinuevo, Jose Luis
AU - Shaw, Leslie M.
AU - Vandijck, Manu
AU - Verbeek, Marcel M.
AU - Savage, Mary
AU - Mattsson, Niklas
AU - Lewczuk, Piotr
AU - Batrla, Richard
AU - Rutz, Sandra
AU - Dean, Robert A.
AU - Blennow, Kaj
N1 - Funding Information:
O.H. is a Wallenberg Clinical Scholar and is supported by grants from the European and Swedish Research Councils. O.H. has acquired research support (for the institution) from Roche, GE Healthcare, Biogen, AVID Radiopharmaceuticals, Fujirebio, and Euroimmun. In the past 2 years, he has received consultancy/speaker fees (paid to the institution) from Lilly, Roche, and Fujirebio. A.M. is an employee of Biogen. A.M.F. is supported by grants from the National Institutes of Health and has received research project funding from Roche Diagnostics, Fujirebio, and Biogen. Dr Fagan is on the Scientific Advisory Boards for Roche Diagnostics, IBL International and AbbVie and consults for Biogen, DiamiR, LabCorp, and Araclon Biotech/Grifols. C.T. serves on the advisory board of Fujirebio and Roche and has performed contract research for Shire, Boehringer, Roche, Probiodrug, PeopleBio, Jansen Prevention Center. She has received grants from the Dutch Research Council (ZonMW), Association of Frontotemporal Dementia/Alzheimer's Drug Discovery Foundation/the Alzheimer's Drug Discovery Foundation, Alzheimer Netherlands, and the Weston Brain Institute. H.Z. is a Wallenberg Academy Fellow and is supported by grants from the Swedish and European Research Councils, as well as the Medical Research Council, UK. H.V. is a co-founder of ADx NeuroSciences and a founder of Biomarkable. J.L.M. acts as a consultant for the following companies: Roche, Roche Diagnostics, Axovant, Lundbeck, General Electric, IBL International, Lilly, Novartis, Otsuka, Oryzon, and MSD and has received competitive funds from the Innovative Medicine Initiative. L.M.S. receives funding from the Alzheimer's Disease Neuroimaging Initiative (ADNI; NIA/NIH grant U19AG024904), MJFox Foundation for Parkinson's Disease Research, Lilly, and Roche. He has provided QC oversight for the Fujirebio INNO-BIA Alz Bio3 immunoassay and currently provides QC oversight for the Roche Elecsys immunoassay for CSF AD biomarkers for the ADNI study. M.V. is an employee of Fujirebio Europe. M.M.V. received funding via Alzheimer Nederland and the CAVIA project (number 733050202), which has been made possible by ZonMW. The CAVIA project is part of “Memorabel” the research and innovation programme for dementia, as part of the Dutch national “Deltaplan for Dementia”: zonmw.nl/dementiaresearch. The CAVIA project is a consortium of Radboudumc, LUMC, Erasmus MC, VUmc, ADx NeuroSciences, Philips Healthcare, Stony Brook University, and Massachusetts General Hospital. M.S. is an employee of Merck and Company, Inc. N.M. received funding from the Swedish Research Council, the Bundy Academy and the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's Disease) at Lund University. P.L. received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement n◦ 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution; he received consultation/lectures honoraria from AJ Roboscreen, IBL International, Fujirebio Europe, and Roche. R.B. and S.R. are current employees of Roche Diagnostics GmbH. K.B. holds the Torsten Söderberg Professorship in Medicine, and is supported by grants from the Swedish Research Council, the Swedish Alzheimer Foundation and the Swedish Brain Foundation.
Publisher Copyright:
© 2018 the Alzheimer's Association
PY - 2018/10
Y1 - 2018/10
N2 - Introduction: Cerebrospinal fluid (CSF) biomarkers have the potential to improve the diagnostic accuracy of Alzheimer's disease, yet there is a lack of harmonized preanalytical CSF handling protocols. Methods: This systematic review summarizes the current literature on the influence of preanalytical variables on CSF biomarker concentration. We evaluated the evidence for three core CSF biomarkers: β-amyloid 42, total tau, and phosphorylated tau. Results: The clinically important variables with the largest amount of conflicting data included the temperature at which samples are stored, the time nonfrozen samples can be stored, and possible effects of additives such as detergents, blood contamination, and centrifugation. Conversely, we discovered that there is consensus that tube material has a significant effect. Discussion: A unified CSF handling protocol is recommended to reduce preanalytical variability and facilitate comparison of CSF biomarkers across studies and laboratories. In future, experiments should use a gold standard with fresh CSF collected in low binding tubes.
AB - Introduction: Cerebrospinal fluid (CSF) biomarkers have the potential to improve the diagnostic accuracy of Alzheimer's disease, yet there is a lack of harmonized preanalytical CSF handling protocols. Methods: This systematic review summarizes the current literature on the influence of preanalytical variables on CSF biomarker concentration. We evaluated the evidence for three core CSF biomarkers: β-amyloid 42, total tau, and phosphorylated tau. Results: The clinically important variables with the largest amount of conflicting data included the temperature at which samples are stored, the time nonfrozen samples can be stored, and possible effects of additives such as detergents, blood contamination, and centrifugation. Conversely, we discovered that there is consensus that tube material has a significant effect. Discussion: A unified CSF handling protocol is recommended to reduce preanalytical variability and facilitate comparison of CSF biomarkers across studies and laboratories. In future, experiments should use a gold standard with fresh CSF collected in low binding tubes.
KW - Alzheimer's disease diagnosis
KW - Biomarkers
KW - Cerebrospinal fluid
KW - Phosphorylated tau
KW - Preanalytical variables
KW - Total tau
KW - β-Amyloid 42
UR - http://www.scopus.com/inward/record.url?scp=85054153726&partnerID=8YFLogxK
U2 - 10.1016/j.jalz.2018.05.008
DO - 10.1016/j.jalz.2018.05.008
M3 - Review article
C2 - 29940161
AN - SCOPUS:85054153726
SN - 1552-5260
VL - 14
SP - 1313
EP - 1333
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 10
ER -