Preanalytical Sample Handling and Sample Stability Testing for the Neurochemical Dementia Diagnostics

Zimmermann, R; Lelental, Natalia; Ganslandt, Oliver; Maler, Juan Manuel; Kornhuber, Johannes; Lewczuk, Piotr

doi:10.3233/jad-2011-110212

Cited by 51 publications

(57 citation statements)

References 12 publications

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“…Bjerke et al (6 ) stated that storage at room temperature for Ͼ24 h did not significantly affect A␤ concentrations in comparison to both fresh samples and storage at Ϫ80°C until analysis. Another study found relatively stable CSF biomarker concentrations even after 4 days, although unsystematic variation increased over time (18 ). In contrast to this, A␤ has been found to decrease during the first 48 h (11 ) or, more in line with the present study, even to increase within 24 h (14 ).…”

Section: Freezing Delaycontrasting

confidence: 56%

“…From long-term stability studies, it is already known that A␤ 1-42 concentrations in samples frozen at Ϫ80°C are stable for at least 2 years (6,18 ), as are concentrations of T-tau and P-tau 181P when stored at Ϫ20°C for at least for 2 and 4 years, respectively (12,18 ). A storage artifact is seen for cystatin C analysis after freezing at Ϫ20°C, but not at Ϫ80°C (24 ).…”

Section: Freezing Temperaturementioning

confidence: 99%

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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 Delaycontrasting

confidence: 56%

Section: Freezing Temperaturementioning

confidence: 99%

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

2015

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“…A small part of the overall variability was caused by within-run variability (CV, ,5%-10%, which is in agreement with previous reports and information from kit vendors regarding assay performance [21][22][23]). The within-laboratory longitudinal variability was larger (CV, 5%-19%), which is also in agreement with previous reports [8,24]. In analysis of variance, between-laboratory variability was a major contributor (19%-28%) to the overall variability.…”

Section: Discussionsupporting

confidence: 81%

P1–178: CSF biomarker variability in the Alzheimer's Association quality control program

Andréasson

Mattsson

Persson

et al. 2013

Alzheimer's & Dementia

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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 (M€ olndal, Sweden) were analyzed by singleanalyte 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.

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“…Considerably, CSF Ab peptides have been reported to be more stable over a storage period of 2-5 days [15,17,18] as measured with distinct methods. These results are in line with our own observations measuring CSF Ab peptides under the conditions of the Ab-SDS-PAGE/immunoblot after samples were stored for up to 48 h. Thus, assay specifications of the Ab-SDS-PAGE/immunoblot are unlikely to account for the reported decrease in Ab peptides after sample storage in plasma and serum.…”

Section: Discussionmentioning

confidence: 99%

Stability of amyloid‐β peptides in plasma and serum

et al. 2012

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Plasma amyloid-β peptide (Aβ) levels have been suggested as a biomarker candidate for detecting incipient AD. Aβ peptides are known to be sensitive to distinct preanalytical sample handling, which calls for standardised preanalytical procedures. We investigated serum and plasma samples of 19 patients with no clinical signs of dementia for different preanalytical sample handlings. Both serum and plasma were analysed by the one-dimensional Aβ-SDS-PAGE/immunoblot, either immediately or after storage at room temperature for 24 and 48 h, respectively. The panel of Aβ1-37/38/39/40/42 and Aβ2-40 was evaluated. In both analytical matrices, sample storage led to a significant loss of measurable peptide levels. This effect was most pronounced during the first 24 h of storage and stronger in serum than in plasma. There were no significant differences between the distinct analysed Aβ peptide species regarding these results. The ratios of peptides (e.g. Aβ1-42/Aβ1-40 and Aβ1-42/Aβ1-38) displayed a higher stability under the influence of storage than each single peptide. In conclusion, plasma may be more appropriate than serum for analysing Aβ peptides for routine application. At least, the analysis should be done within 24 h and peptide ratios should be created to minimise artificial results.

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Preanalytical Sample Handling and Sample Stability Testing for the Neurochemical Dementia Diagnostics

Cited by 51 publications

References 12 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

P1–178: CSF biomarker variability in the Alzheimer's Association quality control program

Stability of amyloid‐β peptides in plasma and serum

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