The CSF biomarkers tau and amyloid ß (Aß) show promise as tools in the diagnostic work-up patients with suspected Alzheimer’s disease (AD) and to monitor treatment effects in AD clinical trials. However, recent multi-center studies have shown that the levels of these CSF biomarkers vary between different research centers and laboratories. This variation in CSF biomarker levels between laboratories complicates multicenter research studies and trials and also precludes the introduction of generally applicable cut-off levels in clinical routine. The variation in CSF biomarker levels between centers is probably the result of variations in pre-analytical procedures (e.g. lumbar puncture procedure and CSF sample processing), analytical procedures, as well as batch-to-batch variation in the biomarker assays.
The aim of the QC program is to standardize CSF biomarker measurements between both research and clinical laboratories. This will increase the analytical precision and improve the longitudinal stability for biomarker measurements. The program will allow direct comparisons of biomarker levels between laboratories and, thus, between publications.
The program is run by the Clinical Neurochemistry Laboratory in Gothenburg, Sweden in conjunction with the Alzheimer's Association. Biotech companies and a number of reference laboratories, including the ADNI biomarker core, are also represented. Both research and clinical CSF laboratories as well as pharmaceutical companies are enrolled in the program.
The Alzheimer’s Association QC program is open for laboratories performing CSF biomarker analyses for clinical diagnosis on a routine basis,
as well as for research laboratories and pharmaceutical companies performing studies on CSF biomarkers in clinical studies or trials on a regular basis.
The program is open for generally (commercially) available assay formats (Innogenetics ELISA and Luminex assays, Meso-Scale assays), but not for in-house assays.The program can be extended to other assays in the future (If you like to participate with another assay use this link).The basic principle is that QC samples (aliquots of pooled CSF) are sent out to the participating laboratories for CSF biomarker analyses, after which biomarkers levels are entered into a report form and returned. In the QC program, 2 different QC samples are sent out to the participating laboratories for each round (3 rounds per year). In addition, one QC sample will be analyzed each round (an aliquot of the same pool), to evaluate the longitudinal stability.
The final report for each QC round includes information on the measured biomarker levels for the individual laboratory and, for comparison, the mean and variation in biomarker levels across all laboratories involved in the program. In addition, the longitudinal stability in CSF biomarker levels for the individual laboratory expressed as percent deviation over time will be reported.
The QC program was launched in November 2009. At present more than 60 laboratories are participating. Two view results from the completed rounds click here.
Kaj Blennow, MD, PhD Henrik Zetterberg, MD, PhD
Professor Ass. Professor
Our paper on measurement variability in the Alzheimer's Association QC program is now published
This paper is based on the first nine rounds of the Alzheimer's Association QC program for CSF biomarkers. Link to abstract at pubmed HERE
It is now time to analyze the May samples (2013-12A, 2013-12B and 2011 QC-L). Please use the new report form version 3.1 when reporting results.
Download the report form HERE.
It is now time to analyze the February samples (2013-11A, 2013-11B and 2011 QC-L). Please use the new report form version 3.1 when reporting results.
Download the report form HERE.
It is now time to analyze the October samples (2012-10A, 2012-10B and 2011 QC-L). Please use the new report form (version 3.0 or 3.1) when reporting results. In November I will start to send samples for next year’s rounds so please check your e-mail in the end of October and remember that no samples will be sent until you confirm that you are able to receive samples the suggested dates.
It is now time to analyze the May samples (2012-9A, 2012-9B and 2011 QC-L). Please use the new report form (version 3.0 or 3.1) when reporting results. There have been a small adjustment in the report form on the sheet for Innogenetics Luminex method, section assay performance we refer to “OD values” where it should have been “FI values” this is corrected in the version 3.1.
Download the report form HERE.
It is soon time to analyze the February samples (2012-8A, 2012-8B and 2011 QC-L) as a part of this programs aim to standardize CSF biomarker measurements we have updated the report form in which we now also ask for information regarding the type of Lab and amount of Kits used every year. Also the assay performance part of the report form has been updated as requested of several participating laboratories. Download the new report form HERE.
It is soon time to analyze the October samples (2011-7A, 2011-7B, QC-L and 2011 QC-L). Note that there are four samples to be analyzed in this round so both the QC-L and 2011 QC-L sample should be analyzed in October. This is because we have to change the longitudinal sample.There is no special report form for this round so you have to fill in two results in one of the boxes just separate the name and results with a backslash.
This paper is based on the first two rounds of the Alzheimer's Association QC program for CSF biomarkers. Link to abstract at pubmed HERE
The manuscript on the external quality control program for CSF biomarkers has now been accepted for publication in Alzheimer’s & Dementia. This manuscript is based on the first two rounds of the Alzheimer's Association QC program for CSF biomarkers.
It is now time to analyze the February samples (2011-6A, 2011-6B and QC-L). For those Labs that haven’t filled in the checklist please do so as soon as conveniently possible. These checklists should be filled in and returned once and then every time a lab decides to change the execution of their assay in any of the points in the checklist.
We are happy to report that the QC program is still growing and we are now over 60 labs registered to participat in the Alz Ass QC program.
It is soon time to analyze the February samples (2011-5A, 2011-5B and QC-L). For those Labs that haven’t filled in the checklist please do so as soon as conveniently possible. These checklists should be filled in and returned once and then every time a lab decides to change the execution of their assay in any of the points in the checklist.
Labs that have not yet received samples for 2011 contact us and we will arrange shipment as soon as possible.
In the new extended report form there have been some uncertainties regarding which values to report due to a not so clear report form.
When reporting OD/FI/ECL values for blank, in the new report form please fill in values before blank subtraction. And reported Max CV% for standard in duplicates should be the highest CV% of any pair of standards calculated using concentration values.
A CSF pool for comparisons between research studies
within the The Alzheimer’s Association QC program.
Read more HERE