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

ABSTRACT: BACKGROUND:The cerebrospinal fluid (CSF) biomarkers amyloid ? (A?)-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 A?, 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 A?-(1-42), P-tau(181P), and T-tau), and 5 used Meso Scale Discovery with the A? triplex (A?N-42, A?N-40, and A?N-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.

SUBMITTER: Mattsson N

PROVIDER: S-EPMC3710290 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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

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

Alzheimer's & dementia : the journal of the Alzheimer's Association 20110701 4

<h4>Background</h4>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 sourc ...[more]

PMID: 21784349

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Project description:Widespread implementation of cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) in clinical settings requires improved accuracy for diagnosis of prodromal disease and for distinguishing AD from non-AD dementias. Novel and promising CSF biomarkers include neurogranin, a marker of synaptic degeneration, and YKL-40, a marker of neuroinflammation.CSF neurogranin and YKL-40 were measured in a cohort of 338 individuals including cognitively healthy controls and patients with stable mild cognitive impairment (sMCI), MCI who later developed AD (MCI-AD), AD dementia, Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), vascular dementia (VaD), and frontotemporal dementia (FTD). The diagnostic accuracy of neurogranin and YKL-40 were compared with the core AD biomarkers, β-amyloid (Aβ42 and Aβ40) and tau.Neurogranin levels were increased in AD and decreased in non-AD dementia compared with healthy controls. As a result, AD patients showed considerably higher CSF levels of neurogranin than DLB/PDD, VaD and FTD patients. CSF YKL-40 levels were increased in AD compared with DLB/PDD but not with VaD or FTD. Neither CSF neurogranin nor YKL-40 levels differed significantly between sMCI patients and MCI-AD patients. Both biomarkers correlated positively with CSF Aβ40 and tau. CSF neurogranin and YKL-40 could separate AD dementia from non-AD dementias (neurogranin, area under the curve [AUC] = 0.761; YKL-40, AUC = 0.604; Aβ42/neurogranin, AUC = 0.849; Aβ42/YKL-40, AUC = 0.785), but the diagnostic accuracy was not better compared to CSF Aβ and tau (Aβ42, AUC = 0.755; tau AUC = 0.858; Aβ42/tau, AUC = 0.895; Aβ42/Aβ40, AUC = 0.881). Similar results were obtained when separating sMCI from MCI-AD cases.CSF neurogranin and YKL-40 do not improve the diagnostic accuracy of either prodromal AD or AD dementia when compared to the core CSF AD biomarkers. Nevertheless, the CSF level of neurogranin is selectively increased in AD dementia, whereas YKL-40 is increased in both AD and FTD suggesting that synaptic degeneration and glial activation may be important in these neurodegenerative conditions.

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

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

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