|Title||The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers.|
|Publication Type||Journal Article|
|Year of Publication||2011|
|Authors||Mattsson, N, Andreasson, U, Persson, S, Arai, H, Batish, SDev, 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, S-K, 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, Q-X, Martins, R, Masters, C, McAuliffe, J, Mercken, M, Moghekar, A, Molinuevo, JLuis, 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|
|Date Published||2011 Jul|
|Keywords||Alzheimer Disease, Amyloid beta-Peptides, Biological Assay, Biomarkers, Enzyme-Linked Immunosorbent Assay, Humans, Peptide Fragments, Phosphorylation, Quality Control, Reproducibility of Results, Sweden, tau Proteins, Time Factors|
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.
|Alternate Journal||Alzheimers Dement|
|PubMed Central ID||PMC3710290|
|Grant List||P01 AG036694 / AG / NIA NIH HHS / United States |
P50 AG005134 / AG / NIA NIH HHS / United States
P50 AG005681 / AG / NIA NIH HHS / United States
U19 AG033655 / AG / NIA NIH HHS / United States