Alzheimer's disease cerebrospinal fluid biomarkers are not influenced by gravity drip or aspiration extraction methodology.

Maree Farrow,S. Lance Macaulay,Sarah Maher,Ralph N. Martins,Brendan Silbert,Rebecca Rumble ,Kelly K. Pertile,Alan Rembach,F.s. Mooney ,Lesley Vidaurre,Christopher Fowler ,David Darby ,James D. Doecke,Colin L. Masters,Stephanie R. Rainey-Smith ,David Ames,Brett Trounson ,Qiao‐Xin Li ,Kevin Taddei,Tabitha Nash,Lisbeth Evered ,Steven Collins ,William J. Wilson

doi:10.1186/s13195-015-0157-7

Abstract

IntroductionCerebrospinal fluid (CSF) biomarkers, although of established utility in the diagnostic evaluation of Alzheimer’s disease (AD), are known to be sensitive to variation based on pre-analytical sample processing. We assessed whether gravity droplet collection versus syringe aspiration was another factor influencing CSF biomarker analyte concentrations and reproducibility.MethodsStandardized lumbar puncture using small calibre atraumatic spinal needles and CSF collection using gravity fed collection followed by syringe aspirated extraction was performed in a sample of elderly individuals participating in a large long-term observational research trial. Analyte assay concentrations were compared.ResultsFor the 44 total paired samples of gravity collection and aspiration, reproducibility was high for biomarker CSF analyte assay concentrations (concordance correlation [95%CI]: beta-amyloid1-42 (Aβ42) 0.83 [0.71 - 0.90]), t-tau 0.99 [0.98 - 0.99], and phosphorylated tau (p-tau) 0.82 [95 % CI 0.71 - 0.89]) and Bonferroni corrected paired sample t-tests showed no significant differences (group means (SD): Aβ42 366.5 (86.8) vs 354.3 (82.6), p = 0.10; t-tau 83.9 (46.6) vs 84.7 (47.4) p = 0.49; p-tau 43.5 (22.8) vs 40.0 (17.7), p = 0.05). The mean duration of collection was 10.9 minutes for gravity collection and <1 minute for aspiration.ConclusionsOur results demonstrate that aspiration of CSF is comparable to gravity droplet collection for AD biomarker analyses but could considerably accelerate throughput and improve the procedural tolerability for assessment of CSF biomarkers.

Highlights

Cerebrospinal fluid (CSF) biomarkers, of established utility in the diagnostic evaluation of Alzheimer’s disease (AD), are known to be sensitive to variation based on pre-analytical sample processing
The CSF in established AD is characterized by a decrease in Aβ42 and increases in total tau (t-tau) and tau phosphorylated at threonine 181 (p-tau)
Of the 54 participant samples, failed quality control for one or more of the multiplexed analytes, with %Percentage coefficient of variance (CV) greater than %. Of these 19, nine samples were rerun and performed with < 20 % %CVs and were included in the final analysis using a total of 44 participant samples

Summary

Introduction

Cerebrospinal fluid (CSF) biomarkers, of established utility in the diagnostic evaluation of Alzheimer’s disease (AD), are known to be sensitive to variation based on pre-analytical sample processing. In 2011, proceedings from the National Institute on Aging - Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease (AD) recommended the addition of biomarkers as an important component of diagnosis [1]. Neuroimaging and cerebrospinal fluid (CSF) sampling are able to identify individuals with high likelihood of AD pathology. The diagnostic performance of these CSF biomarkers to discriminate AD from non-demented older individuals is high, with sensitivity and specificity figures of 80 %–90 % [4]. In addition to the high sensitivity and specificity, CSF analysis has several advantages as a biomarker of choice.

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