The Alzheimer's Association External Quality Control Program for Cerebrospinal Fluid Biomarkers
Authors
- Niklas Mattsson
- Ulf Andreasson
- Staffan Persson
- Hiroyuki Arai
- Sat D. 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
- Harald Hampel
- Aase Handberg
- Michael T. Heneka
- Adrianna Z. Herskovits
- Sanna-Kaisa Herukka
- David M. Holtzmann
- 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, Edith Cowan University
- Albert Llado
- Piotr Lewczuk
- Qiao-Xin Li
- Ralph Martins, Edith Cowan University
- Colin Masters
- John McAullife
- Marc Mercken
- Abhay Moghekar
- Jose 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
- Hikka Soininen
- Johannes Schroder
- 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
Document Type
Journal Article
Keywords
Alzheimer's disease, Cerebrospinal fluid, Biomarkers, External assurance, External control, Proficiency testing
Publisher
Elsevier
Faculty
Faculty of Computing, Health and Science
School
School of Medical Sciences / Centre of Excellence for Alzheimer's Disease Research and Care
RAS ID
13135
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.
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Mattsson, N., Andreasson, U., Persson, S., Arai, H., Batish, S., Bernardini, S.,...Blennow, K. (2011). The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers. Alzheimers and Dementia, 7(4), 386-395. Available here