Risk of Alzheimer's Disease Biological Misdiagnosis Linked to Cerebrospinal Collection Tubes

Perret‐Liaudet, Armand; Pelpel, Mathieu; Tholance, Yannick; Dumont, Benoît; Vanderstichele, Hugo; Zorzi, Willy; Elmoualij, Benaïssa; Schraen, Susanna; Moreaud, Olivier; Gabelle, Audrey; Thouvenot, Éric; Thomas‐Antérion, Catherine; Touchon, Jacques; Krolak‐Salmon, Pierre; Kovács, Gábor G.; Coudreuse, Arnaud; Quadrio, Isabelle; Lehmann, Sylvain

doi:10.3233/jad-2012-120361

Cited by 97 publications

(91 citation statements)

References 18 publications

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“…The fact that long-term studies show stable concentrations for all 3 biomarkers means that differences between liquid N 2 , Ϫ80°C, and Ϫ20°C are most likely attributable to the initial freezing conditions. This is also seen for tubes that immediately adsorb A␤ (25 ).…”

Section: Freezing Temperaturementioning

confidence: 54%

Importance and Impact of Preanalytical Variables on Alzheimer Disease Biomarker Concentrations in Cerebrospinal Fluid

2015

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BACKGROUND Analyses of cerebrospinal fluid (CSF) biomarkers (β-amyloid protein, total tau protein, and hyperphosphorylated tau protein) are part of the diagnostic criteria of Alzheimer disease. Different preanalytical sample procedures contribute to variability of CSF biomarker concentrations, hampering between-laboratory comparisons. The aim of this study was to explore the influence of fractionated sampling, centrifugation, freezing temperature, freezing delay, and freeze–thaw cycles on CSF biomarker analyses. METHODS We studied fractionated sampling in sequential aliquots of lumbar CSF. Centrifuged and noncentrifuged samples from the same fraction were compared. CSF samples were subjected to different protocols (liquid nitrogen, −80 °C, and −20 °C; 24 h at 2–8 °C; and 24 and 48 h at room temperature). To study the influence of freeze–thaw cycles, samples were thawed up to 4 times and refrozen at −80 °C. CSF was collected in polypropylene tubes. We measured CSF biomarker concentrations with commercially available single-analyte Innotest assays. RESULTS CSF biomarker concentrations from non–blood-contaminated samples are not influenced by centrifugation or fractionated sampling. Freezing temperature and delayed storage can affect biomarker concentrations; freezing of CSF samples at −80 °C as soon as possible after collection is recommended. Consecutive freezing and thawing of CSF samples up to 3 times had little effect. CONCLUSIONS Temperature of freezing, delay until freezing, and freeze–thaw cycles significantly influence CSF biomarker concentrations, stressing the need for standard operating procedures for preanalytical sample handling. The differences observed in this study are, however, relatively small, and the impact on the clinical value of these CSF biomarkers needs to be determined.

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Section: Freezing Temperaturementioning

confidence: 54%

Importance and Impact of Preanalytical Variables on Alzheimer Disease Biomarker Concentrations in Cerebrospinal Fluid

2015

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“…Very impressive are the results of a study published last year that dealt with the influence of the material of the sample tubes on the measurement results [16,17] . The concentrations of tau protein, phospho-tau protein and A β 1 -42 were investigated in dependence on the sample tubes used, for a total of 11 different types of tubes.…”

Section: Pre-analytical and Analytical Issues In The Determination Ofmentioning

confidence: 83%

Biomarkers for neurological disorders – call for standardization

Torzewski

2014

LaboratoriumsMedizin

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With increasing life expectancy, neurodegenerative diseases such as Alzheimer ' s disease (AD) and Parkinson ' s disease (PD), as well as neurovascular diseases such as cerebral ischemia, are becoming a rapidly growing worldwide problem causing an increased burden on society. The development of biomarkers is aimed to enable the identification of at-risk individuals, enable early diagnosis, and reflect the progression of disease. Future challenges refer to the need for standardization of known biomarkers on the one hand and the identification of new biomarkers on the other hand. The former is impressively exemplified by a recent study addressing the impact of various types of cerebrospinal fluid collection tubes for detection of total tau, phosphorylated tau, and β -amyloid 1 -42 on the diagnosis of AD. This issue was identified as a key issue by the Alzheimer ' s Biomarkers Standardization Initiative (ABSI) and recommendations were listed which should be used to enable better standardization between laboratories and enable results for the AD biomarkers to be comparable between different sites. The latter challenge in particular concerns PD and is addressed by the Parkinson Progression Marker Initiative (PPMI), a comprehensive observational, international, multi-center study designed to identify PD progression biomarkers both to improve understanding of disease etiology and course and to provide crucial tools to enhance the likelihood of success of PD modifying therapeutic trials. With regard to cerebral ischemia, at present there are no clinically validated biomarkers. Nevertheless, the development of a clinically validated biomarker of acute cerebral ischemia would have the potential to facilitate the use of time-sensitive reperfusion strategies, allow for individualization of patient care by predicting relative risk of hemorrhage and volume of penumbral tissue, and add valuable prognostic information for patients presenting with acute stroke. Thereby, it is expected that a panel of biomarkers rather than one single marker will meet these criteria in the future. Unlike cerebral ischemia, cerebral hemorrhage biomarkers will probably be limited to the assessment of prognosis in the course of the disease.

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“…The consequences on AD biological diagnosis could be very important, as demonstrated in a multisite study conducted in four French Centers for Memory Research and Resources (CMRR) (Montpellier, Lille, Lyon and Paris) [33]. Standardization of the collection tubes (using, e.g., the tube Sarstedt 62.610.201) could improve multicenter comparison and decrease the risk of wrong diagnosis [34].…”

Section: Csf Collection Tubesmentioning

confidence: 99%

Quantitative detection of amyloid-β peptides by mass spectrometry: state of the art and clinical applications

Bros¹,

Delatour

Vialaret

et al. 2015

Clinical Chemistry and Laboratory Medicine (CCLM)

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Alzheimer's disease (AD) is the most common form of dementia in humans, and a major public health concern with 35 million of patients worldwide. Cerebrospinal fluid (CSF) biomarkers being early diagnostic indicators of AD, it is essential to use the most efficient analytical methods to detect and quantify them accurately. These biomarkers, and more specifically amyloid-β (Aβ) peptides, are measured in routine clinical practice using immunoassays. However, there are several limits to this immunodetection in terms of specificity and multiplexing of the multiple isoforms of the Aβ peptides. To overcome these issues, the quantification of these analytes by mass spectrometry (MS) represents an interesting alternative, and several assays have been described over the past years. This article reviews the different Aβ peptides quantitative MS-based approaches published so far, compares their pre-analytical phase, and the different quantitative strategies implemented that might be suitable for clinical applications.

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Risk of Alzheimer's Disease Biological Misdiagnosis Linked to Cerebrospinal Collection Tubes

Cited by 97 publications

References 18 publications

Importance and Impact of Preanalytical Variables on Alzheimer Disease Biomarker Concentrations in Cerebrospinal Fluid

Importance and Impact of Preanalytical Variables on Alzheimer Disease Biomarker Concentrations in Cerebrospinal Fluid

Biomarkers for neurological disorders – call for standardization

Quantitative detection of amyloid-β peptides by mass spectrometry: state of the art and clinical applications

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