The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers

Niklas Mattsson, Ulf Andreasson, Staffan Persson, Hiroyuki Arai, Sat Dev Batish, Sergio Bernardini, Luisella Bocchio-Chiavetto, Marinus A. Blankenstein, Maria C. Carrillo, Sonia Chalbot, Els Coart, Davide Chiasserini, Neal Cutler, Gunilla Dahlfors, Stefan Duller, Anne M. Fagan, Orestes Forlenza, Giovanni B. Frisoni, Douglas Galasko, Daniela Galimberti & 58 others Harald Hampel, Aase Handberg, Michael T. Heneka, Adrianna Z. Herskovits, Sanna Kaisa Herukka, David M. Holtzman, Christian Humpel, Bradley T. Hyman, Khalid Iqbal, Mathias Jucker, Stephan A. Kaeser, Elmar Kaiser, Elisabeth Kapaki, Daniel Kidd, Peter Klivenyi, Cindy S. Knudsen, Markus P. Kummer, James Lui, Albert Lladó, Piotr Lewczuk, Qiao Xin Li, Ralph Martins, Colin Masters, John McAuliffe, Marc Mercken, Abhay R Moghekar, José Luis Molinuevo, Thomas J. Montine, William Nowatzke, Richard O'Brien, Markus Otto, George P. Paraskevas, Lucilla Parnetti, Ronald C. Petersen, David Prvulovic, Herman P M De Reus, Robert A. Rissman, Elio Scarpini, Alessandro Stefani, Hilkka Soininen, Johannes Schröder, Leslie M. Shaw, Anders Skinningsrud, Brith Skrogstad, Annette Spreer, Leda Talib, Charlotte Teunissen, John Q. Trojanowski, Hayrettin Tumani, Robert M. Umek, Bianca Van Broeck, Hugo Vanderstichele, Laszlo Vecsei, Marcel M. Verbeek, Manfred Windisch, Jing Zhang, Henrik Zetterberg, Kaj Blennow

Research output: Contribution to journalArticle

Abstract

Background: The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program. Methods: The program is open for laboratories using commercially available kits for Aβ, T-tau, or P-tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Mölndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples. Results: Forty laboratories participated. Twenty-six used INNOTEST enzyme-linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO-BIA AlzBio3 kit (both measure Aβ-(1-42), P-tau(181P), and T-tau), and 5 used Meso Scale Discovery with the Aβ triplex (AβN-42, AβN-40, and AβN-38) or T-tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within-laboratory precisions differed considerably between biomarkers within individual laboratories. Conclusions: Measurements of CSF AD biomarkers show large between-laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers.

Original languageEnglish (US)
JournalAlzheimer's and Dementia
Volume7
Issue number4
DOIs
StatePublished - Jul 2011

Fingerprint

Quality Control
Cerebrospinal Fluid
Biomarkers
Alzheimer Disease
Neurochemistry
Amyloid
Sweden
Enzyme-Linked Immunosorbent Assay

Keywords

  • Alzheimer's disease
  • Biomarkers
  • Cerebrospinal fluid
  • External assurance
  • External control
  • Proficiency testing

ASJC Scopus subject areas

  • Health Policy
  • Epidemiology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience
  • Clinical Neurology

Cite this

Mattsson, N., Andreasson, U., Persson, S., Arai, H., Batish, S. D., Bernardini, S., ... Blennow, K. (2011). The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers. Alzheimer's and Dementia, 7(4). https://doi.org/10.1016/j.jalz.2011.05.2243

The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers. / Mattsson, Niklas; Andreasson, Ulf; Persson, Staffan; Arai, Hiroyuki; Batish, Sat Dev; Bernardini, Sergio; Bocchio-Chiavetto, Luisella; Blankenstein, Marinus A.; Carrillo, Maria C.; Chalbot, Sonia; Coart, Els; Chiasserini, Davide; Cutler, Neal; Dahlfors, Gunilla; Duller, Stefan; Fagan, Anne M.; Forlenza, Orestes; Frisoni, Giovanni B.; Galasko, Douglas; Galimberti, Daniela; Hampel, Harald; Handberg, Aase; Heneka, Michael T.; Herskovits, Adrianna Z.; Herukka, Sanna Kaisa; Holtzman, David M.; Humpel, Christian; Hyman, Bradley T.; Iqbal, Khalid; Jucker, Mathias; Kaeser, Stephan A.; Kaiser, Elmar; Kapaki, Elisabeth; Kidd, Daniel; Klivenyi, Peter; Knudsen, Cindy S.; Kummer, Markus P.; Lui, James; Lladó, Albert; Lewczuk, Piotr; Li, Qiao Xin; Martins, Ralph; Masters, Colin; McAuliffe, John; Mercken, Marc; Moghekar, Abhay R; Molinuevo, José Luis; Montine, Thomas J.; Nowatzke, William; O'Brien, Richard; Otto, Markus; Paraskevas, George P.; Parnetti, Lucilla; Petersen, Ronald C.; Prvulovic, David; De Reus, Herman P M; Rissman, Robert A.; Scarpini, Elio; Stefani, Alessandro; Soininen, Hilkka; Schröder, Johannes; Shaw, Leslie M.; Skinningsrud, Anders; Skrogstad, Brith; Spreer, Annette; Talib, Leda; Teunissen, Charlotte; Trojanowski, John Q.; Tumani, Hayrettin; Umek, Robert M.; Van Broeck, Bianca; Vanderstichele, Hugo; Vecsei, Laszlo; Verbeek, Marcel M.; Windisch, Manfred; Zhang, Jing; Zetterberg, Henrik; Blennow, Kaj.

In: Alzheimer's and Dementia, Vol. 7, No. 4, 07.2011.

Research output: Contribution to journalArticle

Mattsson, N, Andreasson, U, Persson, S, Arai, H, Batish, SD, Bernardini, S, Bocchio-Chiavetto, L, Blankenstein, MA, Carrillo, 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, AR, Molinuevo, JL, Montine, TJ, Nowatzke, W, O'Brien, R, Otto, M, Paraskevas, GP, Parnetti, L, Petersen, RC, Prvulovic, D, De Reus, HPM, Rissman, RA, Scarpini, E, Stefani, A, Soininen, H, Schröder, J, Shaw, LM, Skinningsrud, A, Skrogstad, B, Spreer, A, Talib, L, Teunissen, 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', Alzheimer's and Dementia, vol. 7, no. 4. https://doi.org/10.1016/j.jalz.2011.05.2243
Mattsson, Niklas ; Andreasson, Ulf ; Persson, Staffan ; Arai, Hiroyuki ; Batish, Sat Dev ; Bernardini, Sergio ; Bocchio-Chiavetto, Luisella ; Blankenstein, Marinus A. ; Carrillo, Maria C. ; Chalbot, Sonia ; Coart, Els ; Chiasserini, Davide ; Cutler, Neal ; Dahlfors, Gunilla ; Duller, Stefan ; Fagan, Anne M. ; Forlenza, Orestes ; Frisoni, Giovanni B. ; Galasko, Douglas ; Galimberti, Daniela ; Hampel, Harald ; Handberg, Aase ; Heneka, Michael T. ; Herskovits, Adrianna Z. ; Herukka, Sanna Kaisa ; Holtzman, David M. ; Humpel, Christian ; Hyman, Bradley T. ; Iqbal, Khalid ; Jucker, Mathias ; Kaeser, Stephan A. ; Kaiser, Elmar ; Kapaki, Elisabeth ; Kidd, Daniel ; Klivenyi, Peter ; Knudsen, Cindy S. ; Kummer, Markus P. ; Lui, James ; Lladó, Albert ; Lewczuk, Piotr ; Li, Qiao Xin ; Martins, Ralph ; Masters, Colin ; McAuliffe, John ; Mercken, Marc ; Moghekar, Abhay R ; Molinuevo, José Luis ; Montine, Thomas J. ; Nowatzke, William ; O'Brien, Richard ; Otto, Markus ; Paraskevas, George P. ; Parnetti, Lucilla ; Petersen, Ronald C. ; Prvulovic, David ; De Reus, Herman P M ; Rissman, Robert A. ; Scarpini, Elio ; Stefani, Alessandro ; Soininen, Hilkka ; Schröder, Johannes ; Shaw, Leslie M. ; Skinningsrud, Anders ; Skrogstad, Brith ; Spreer, Annette ; Talib, Leda ; Teunissen, Charlotte ; Trojanowski, John Q. ; Tumani, Hayrettin ; Umek, Robert M. ; Van Broeck, Bianca ; Vanderstichele, Hugo ; Vecsei, Laszlo ; Verbeek, Marcel M. ; Windisch, Manfred ; Zhang, Jing ; Zetterberg, Henrik ; Blennow, Kaj. / The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers. In: Alzheimer's and Dementia. 2011 ; Vol. 7, No. 4.
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title = "The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers",
abstract = "Background: The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program. Methods: The program is open for laboratories using commercially available kits for Aβ, T-tau, or P-tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the M{\"o}lndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples. Results: Forty laboratories participated. Twenty-six used INNOTEST enzyme-linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO-BIA AlzBio3 kit (both measure Aβ-(1-42), P-tau(181P), and T-tau), and 5 used Meso Scale Discovery with the Aβ triplex (AβN-42, AβN-40, and AβN-38) or T-tau kits. The total coefficients of variation between the laboratories were 13{\%} to 36{\%}. Five laboratories analyzed the samples six times on different occasions. Within-laboratory precisions differed considerably between biomarkers within individual laboratories. Conclusions: Measurements of CSF AD biomarkers show large between-laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers.",
keywords = "Alzheimer's disease, Biomarkers, Cerebrospinal fluid, External assurance, External control, Proficiency testing",
author = "Niklas Mattsson and Ulf Andreasson and Staffan Persson and Hiroyuki Arai and Batish, {Sat Dev} and Sergio Bernardini and Luisella Bocchio-Chiavetto and Blankenstein, {Marinus A.} and Carrillo, {Maria C.} and Sonia Chalbot and Els Coart and Davide Chiasserini and Neal Cutler and Gunilla Dahlfors and Stefan Duller and Fagan, {Anne M.} and Orestes Forlenza and Frisoni, {Giovanni B.} and Douglas Galasko and Daniela Galimberti and Harald Hampel and Aase Handberg and Heneka, {Michael T.} and Herskovits, {Adrianna Z.} and Herukka, {Sanna Kaisa} and Holtzman, {David M.} and Christian Humpel and Hyman, {Bradley T.} and Khalid Iqbal and Mathias Jucker and Kaeser, {Stephan A.} and Elmar Kaiser and Elisabeth Kapaki and Daniel Kidd and Peter Klivenyi and Knudsen, {Cindy S.} and Kummer, {Markus P.} and James Lui and Albert Llad{\'o} and Piotr Lewczuk and Li, {Qiao Xin} and Ralph Martins and Colin Masters and John McAuliffe and Marc Mercken and Moghekar, {Abhay R} and Molinuevo, {Jos{\'e} Luis} and Montine, {Thomas J.} and William Nowatzke and Richard O'Brien and Markus Otto and Paraskevas, {George P.} and Lucilla Parnetti and Petersen, {Ronald C.} and David Prvulovic and {De Reus}, {Herman P M} and Rissman, {Robert A.} and Elio Scarpini and Alessandro Stefani and Hilkka Soininen and Johannes Schr{\"o}der and Shaw, {Leslie M.} and Anders Skinningsrud and Brith Skrogstad and Annette Spreer and Leda Talib and Charlotte Teunissen and Trojanowski, {John Q.} and Hayrettin Tumani and Umek, {Robert M.} and {Van Broeck}, Bianca and Hugo Vanderstichele and Laszlo Vecsei and Verbeek, {Marcel M.} and Manfred Windisch and Jing Zhang and Henrik Zetterberg and Kaj Blennow",
year = "2011",
month = "7",
doi = "10.1016/j.jalz.2011.05.2243",
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volume = "7",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
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TY - JOUR

T1 - The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers

AU - Mattsson, Niklas

AU - Andreasson, Ulf

AU - Persson, Staffan

AU - Arai, Hiroyuki

AU - Batish, Sat Dev

AU - Bernardini, Sergio

AU - Bocchio-Chiavetto, Luisella

AU - Blankenstein, Marinus A.

AU - Carrillo, Maria C.

AU - Chalbot, Sonia

AU - Coart, Els

AU - Chiasserini, Davide

AU - Cutler, Neal

AU - Dahlfors, Gunilla

AU - Duller, Stefan

AU - Fagan, Anne M.

AU - Forlenza, Orestes

AU - Frisoni, Giovanni B.

AU - Galasko, Douglas

AU - Galimberti, Daniela

AU - Hampel, Harald

AU - Handberg, Aase

AU - Heneka, Michael T.

AU - Herskovits, Adrianna Z.

AU - Herukka, Sanna Kaisa

AU - Holtzman, David M.

AU - Humpel, Christian

AU - Hyman, Bradley T.

AU - Iqbal, Khalid

AU - Jucker, Mathias

AU - Kaeser, Stephan A.

AU - Kaiser, Elmar

AU - Kapaki, Elisabeth

AU - Kidd, Daniel

AU - Klivenyi, Peter

AU - Knudsen, Cindy S.

AU - Kummer, Markus P.

AU - Lui, James

AU - Lladó, Albert

AU - Lewczuk, Piotr

AU - Li, Qiao Xin

AU - Martins, Ralph

AU - Masters, Colin

AU - McAuliffe, John

AU - Mercken, Marc

AU - Moghekar, Abhay R

AU - Molinuevo, José Luis

AU - Montine, Thomas J.

AU - Nowatzke, William

AU - O'Brien, Richard

AU - Otto, Markus

AU - Paraskevas, George P.

AU - Parnetti, Lucilla

AU - Petersen, Ronald C.

AU - Prvulovic, David

AU - De Reus, Herman P M

AU - Rissman, Robert A.

AU - Scarpini, Elio

AU - Stefani, Alessandro

AU - Soininen, Hilkka

AU - Schröder, Johannes

AU - Shaw, Leslie M.

AU - Skinningsrud, Anders

AU - Skrogstad, Brith

AU - Spreer, Annette

AU - Talib, Leda

AU - Teunissen, Charlotte

AU - Trojanowski, John Q.

AU - Tumani, Hayrettin

AU - Umek, Robert M.

AU - Van Broeck, Bianca

AU - Vanderstichele, Hugo

AU - Vecsei, Laszlo

AU - Verbeek, Marcel M.

AU - Windisch, Manfred

AU - Zhang, Jing

AU - Zetterberg, Henrik

AU - Blennow, Kaj

PY - 2011/7

Y1 - 2011/7

N2 - Background: The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program. Methods: The program is open for laboratories using commercially available kits for Aβ, T-tau, or P-tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Mölndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples. Results: Forty laboratories participated. Twenty-six used INNOTEST enzyme-linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO-BIA AlzBio3 kit (both measure Aβ-(1-42), P-tau(181P), and T-tau), and 5 used Meso Scale Discovery with the Aβ triplex (AβN-42, AβN-40, and AβN-38) or T-tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within-laboratory precisions differed considerably between biomarkers within individual laboratories. Conclusions: Measurements of CSF AD biomarkers show large between-laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers.

AB - Background: The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program. Methods: The program is open for laboratories using commercially available kits for Aβ, T-tau, or P-tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Mölndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples. Results: Forty laboratories participated. Twenty-six used INNOTEST enzyme-linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO-BIA AlzBio3 kit (both measure Aβ-(1-42), P-tau(181P), and T-tau), and 5 used Meso Scale Discovery with the Aβ triplex (AβN-42, AβN-40, and AβN-38) or T-tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within-laboratory precisions differed considerably between biomarkers within individual laboratories. Conclusions: Measurements of CSF AD biomarkers show large between-laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers.

KW - Alzheimer's disease

KW - Biomarkers

KW - Cerebrospinal fluid

KW - External assurance

KW - External control

KW - Proficiency testing

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