The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers
Authors: 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 , 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 
Published: July 2011

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.