Document Detail


CSF biomarker variability in the Alzheimer's Association quality control program.
MedLine Citation:
PMID:  23622690     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The cerebrospinal fluid (CSF) biomarkers amyloid beta 1-42, total tau, and phosphorylated tau are used increasingly for Alzheimer's disease (AD) research and patient management. However, there are large variations in biomarker measurements among and within laboratories.
METHODS: Data from the first nine rounds of the Alzheimer's Association quality control program was used to define the extent and sources of analytical variability. In each round, three CSF samples prepared at the Clinical Neurochemistry Laboratory (Mölndal, Sweden) were analyzed by single-analyte enzyme-linked immunosorbent assay (ELISA), a multiplexing xMAP assay, or an immunoassay with electrochemoluminescence detection.
RESULTS: A total of 84 laboratories participated. Coefficients of variation (CVs) between laboratories were around 20% to 30%; within-run CVs, less than 5% to 10%; and longitudinal within-laboratory CVs, 5% to 19%. Interestingly, longitudinal within-laboratory CV differed between biomarkers at individual laboratories, suggesting that a component of it was assay dependent. Variability between kit lots and between laboratories both had a major influence on amyloid beta 1-42 measurements, but for total tau and phosphorylated tau, between-kit lot effects were much less than between-laboratory effects. Despite the measurement variability, the between-laboratory consistency in classification of samples (using prehoc-derived cutoffs for AD) was high (>90% in 15 of 18 samples for ELISA and in 12 of 18 samples for xMAP).
CONCLUSIONS: The overall variability remains too high to allow assignment of universal biomarker cutoff values for a specific intended use. Each laboratory must ensure longitudinal stability in its measurements and use internally qualified cutoff levels. Further standardization of laboratory procedures and improvement of kit performance will likely increase the usefulness of CSF AD biomarkers for researchers and clinicians.
Authors:
Niklas Mattsson; Ulf Andreasson; Staffan Persson; Maria C Carrillo; Steven Collins; Sonia Chalbot; Neal Cutler; Diane Dufour-Rainfray; Anne M Fagan; Niels H H Heegaard; Ging-Yuek Robin Hsiung; Bradley Hyman; Khalid Iqbal; D Richard Lachno; Alberto Lleó; Piotr Lewczuk; José L Molinuevo; Piero Parchi; Axel Regeniter; Robert Rissman; Hanna Rosenmann; Giuseppe Sancesario; Johannes Schröder; Leslie M Shaw; Charlotte E Teunissen; John Q Trojanowski; Hugo Vanderstichele; Manu Vandijck; Marcel M Verbeek; Henrik Zetterberg; Kaj Blennow; Stephan A Käser;
Publication Detail:
Type:  Journal Article; Validation Studies    
Journal Detail:
Title:  Alzheimer's & dementia : the journal of the Alzheimer's Association     Volume:  9     ISSN:  1552-5279     ISO Abbreviation:  Alzheimers Dement     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-29     Completed Date:  2013-10-22     Revised Date:  2014-03-26    
Medline Journal Info:
Nlm Unique ID:  101231978     Medline TA:  Alzheimers Dement     Country:  United States    
Other Details:
Languages:  eng     Pagination:  251-61     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Alzheimer Disease / cerebrospinal fluid*,  diagnosis*
Amyloid beta-Peptides / cerebrospinal fluid
Biological Markers / cerebrospinal fluid*
Chemistry, Clinical / standards*
Enzyme-Linked Immunosorbent Assay / standards*
Humans
Laboratories, Hospital / standards*
Peptide Fragments / cerebrospinal fluid
Phosphorylation
Quality Control
Reproducibility of Results
Societies, Medical / standards
tau Proteins / cerebrospinal fluid
Grant Support
ID/Acronym/Agency:
P01 AG026276/AG/NIA NIH HHS; P50 AG005134/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Amyloid beta-Peptides; 0/Biological Markers; 0/Peptide Fragments; 0/amyloid beta-protein (1-42); 0/tau Proteins
Investigator
Investigator/Affiliation:
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 / ; Harald Hampel / ; Aase Handberg / ; Michael T Heneka / ; Adrianna Z Herskovits / ; Sanna-Kaisa Herukka / ; David M Holtzman / ; Christian Humpel / ; Bradley T Hyman / ; Khalid Iqbal / ; Mathias Jukcer / ; Stephan A Kaeser / ; Elmar Kaiser / ; Elisabeth Kapaki / ; Daniel Kidd / ; Peter Klivenyi / ; Cindy S Knudsen / ; Markus P Kummer / ; James Lui / ; Albert Lladó / ; Piotr Lewezuk / ; Qiao-Xin Li / ; Ralph Martins / ; Colin Masters / ; John McAuliffe / ; Marc Mercken / ; Abhay 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 /

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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