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Published in: Alzheimer's Research & Therapy 1/2015

Open Access 01-12-2015 | Research

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

Authors: Alan Rembach, Lisbeth A. Evered, Qiao-Xin Li, Tabitha Nash, Lesley Vidaurre, Christopher J. Fowler, Kelly K. Pertile, Rebecca L. Rumble, Brett O. Trounson, Sarah Maher, Francis Mooney, Maree Farrow, Kevin Taddei, Stephanie Rainey-Smith, Simon M. Laws, S. Lance Macaulay, William Wilson, David G. Darby, Ralph N. Martins, David Ames, Steven Collins, Brendan Silbert, Colin L. Masters, James D. Doecke, the AIBL Research Group

Published in: Alzheimer's Research & Therapy | Issue 1/2015

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Abstract

Introduction

Cerebrospinal 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.

Methods

Standardized 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.

Results

For 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.

Conclusions

Our 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.
Literature
1.
go back to reference Jack Jr CR, Albert MS, Knopman DS, McKhann GM, Sperling RA, Carrillo MC, et al. Introduction to the recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7:257–62.PubMedCentralCrossRefPubMed Jack Jr CR, Albert MS, Knopman DS, McKhann GM, Sperling RA, Carrillo MC, et al. Introduction to the recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7:257–62.PubMedCentralCrossRefPubMed
2.
go back to reference Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, et al. Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study. Lancet Neurol. 2013;12:357–67.CrossRefPubMed Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, et al. Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study. Lancet Neurol. 2013;12:357–67.CrossRefPubMed
3.
go back to reference Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, et al. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med. 2012;367:795–804.PubMedCentralCrossRefPubMed Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, et al. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med. 2012;367:795–804.PubMedCentralCrossRefPubMed
4.
go back to reference Blennow K, Hampel H. CSF markers for incipient Alzheimer's disease. Lancet Neurol. 2003;2:605–13.CrossRefPubMed Blennow K, Hampel H. CSF markers for incipient Alzheimer's disease. Lancet Neurol. 2003;2:605–13.CrossRefPubMed
6.
go back to reference Williams JL, Umapathi T. Diagnostic lumbar puncture: minimizing complications. Intern Med J. 2008;38:587–91.CrossRefPubMed Williams JL, Umapathi T. Diagnostic lumbar puncture: minimizing complications. Intern Med J. 2008;38:587–91.CrossRefPubMed
7.
go back to reference Zetterberg H, Tullhog K, Hansson O, Minthon L, Londos E, Blennow K. Low incidence of post-lumbar puncture headache in 1,089 consecutive memory clinic patients. Eur Neurol. 2010;63:326–30.CrossRefPubMed Zetterberg H, Tullhog K, Hansson O, Minthon L, Londos E, Blennow K. Low incidence of post-lumbar puncture headache in 1,089 consecutive memory clinic patients. Eur Neurol. 2010;63:326–30.CrossRefPubMed
8.
go back to reference Hort J, Bartos A, Pirttila T, Scheltens P. Use of cerebrospinal fluid biomarkers in diagnosis of dementia across Europe. Eur J Neurol. 2010;17:90–6.CrossRefPubMed Hort J, Bartos A, Pirttila T, Scheltens P. Use of cerebrospinal fluid biomarkers in diagnosis of dementia across Europe. Eur J Neurol. 2010;17:90–6.CrossRefPubMed
9.
go back to reference Mattsson N, Andreasson U, Persson S, Carrillo MC, Collins S, Chalbot S, et al. CSF biomarker variability in the Alzheimer's Association quality control program. Alzheimers Dement. 2013;9:251–61.PubMedCentralCrossRefPubMed Mattsson N, Andreasson U, Persson S, Carrillo MC, Collins S, Chalbot S, et al. CSF biomarker variability in the Alzheimer's Association quality control program. Alzheimers Dement. 2013;9:251–61.PubMedCentralCrossRefPubMed
10.
go back to reference Vanderstichele H, Bibl M, Engelborghs S, Le Bastard N, Lewczuk P, Molinuevo JL, et al. Standardization of preanalytical aspects of cerebrospinal fluid biomarker testing for Alzheimer's disease diagnosis: a consensus paper from the Alzheimer's Biomarkers Standardization Initiative. Alzheimers Dement. 2012;8:65–73.CrossRefPubMed Vanderstichele H, Bibl M, Engelborghs S, Le Bastard N, Lewczuk P, Molinuevo JL, et al. Standardization of preanalytical aspects of cerebrospinal fluid biomarker testing for Alzheimer's disease diagnosis: a consensus paper from the Alzheimer's Biomarkers Standardization Initiative. Alzheimers Dement. 2012;8:65–73.CrossRefPubMed
11.
go back to reference Fagan AM, Shaw LM, Xiong C, Vanderstichele H, Mintun MA, Trojanowski JQ, et al. Comparison of analytical platforms for cerebrospinal fluid measures of beta-amyloid 1–42, total tau, and p-tau181 for identifying Alzheimer disease amyloid plaque pathology. Arch Neurol. 2011;68:1137–44.PubMedCentralCrossRefPubMed Fagan AM, Shaw LM, Xiong C, Vanderstichele H, Mintun MA, Trojanowski JQ, et al. Comparison of analytical platforms for cerebrospinal fluid measures of beta-amyloid 1–42, total tau, and p-tau181 for identifying Alzheimer disease amyloid plaque pathology. Arch Neurol. 2011;68:1137–44.PubMedCentralCrossRefPubMed
12.
go back to reference Ellis KA, Bush AI, Darby D, De Fazio D, Foster J, Hudson P, et al. The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging: methodology and baseline characteristics of 1112 individuals recruited for a longitudinal study of Alzheimer's disease. Int Psychogeriatr. 2009;21:672–87.CrossRefPubMed Ellis KA, Bush AI, Darby D, De Fazio D, Foster J, Hudson P, et al. The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging: methodology and baseline characteristics of 1112 individuals recruited for a longitudinal study of Alzheimer's disease. Int Psychogeriatr. 2009;21:672–87.CrossRefPubMed
13.
go back to reference Swallow DM, Fellner N, Varsos GV, Czosnyka M, Smielewski P, Pickard JD, et al. Repeatability of cerebrospinal fluid constant rate infusion study. Acta Neurol Scand. 2014;130:131–8.CrossRefPubMed Swallow DM, Fellner N, Varsos GV, Czosnyka M, Smielewski P, Pickard JD, et al. Repeatability of cerebrospinal fluid constant rate infusion study. Acta Neurol Scand. 2014;130:131–8.CrossRefPubMed
14.
go back to reference Corbey MP, Bach AB, Lech K, Frorup AM. Grading of severity of postdural puncture headache after 27-gauge Quincke and Whitacre needles. Acta Anaesthesiol Scand. 1997;41:779–84.CrossRefPubMed Corbey MP, Bach AB, Lech K, Frorup AM. Grading of severity of postdural puncture headache after 27-gauge Quincke and Whitacre needles. Acta Anaesthesiol Scand. 1997;41:779–84.CrossRefPubMed
15.
go back to reference Monserrate AE, Ryman DC, Ma S, Xiong C, Noble JM, Ringman JM, et al. Factors associated with the onset and persistence of post-lumbar puncture headache. JAMA Neurol. 2015;72:325–32.CrossRefPubMed Monserrate AE, Ryman DC, Ma S, Xiong C, Noble JM, Ringman JM, et al. Factors associated with the onset and persistence of post-lumbar puncture headache. JAMA Neurol. 2015;72:325–32.CrossRefPubMed
16.
go back to reference Gorelick PB, Biller J. Lumbar puncture. Technique, indications, and complications. Postgrad Med. 1986;79:257–68.PubMed Gorelick PB, Biller J. Lumbar puncture. Technique, indications, and complications. Postgrad Med. 1986;79:257–68.PubMed
17.
go back to reference Perret-Liaudet A, Pelpel M, Tholance Y, Dumont B, Vanderstichele H, Zorzi W, et al. Risk of Alzheimer's disease biological misdiagnosis linked to cerebrospinal collection tubes. J Alzheimers Dis. 2012;31:13–20.PubMed Perret-Liaudet A, Pelpel M, Tholance Y, Dumont B, Vanderstichele H, Zorzi W, et al. Risk of Alzheimer's disease biological misdiagnosis linked to cerebrospinal collection tubes. J Alzheimers Dis. 2012;31:13–20.PubMed
18.
go back to reference Davis A, Dobson R, Kaninia S, Espasandin M, Berg A, Giovannoni G, et al. Change practice now! Using atraumatic needles to prevent post lumbar puncture headache. Eur J Neurol. 2014;21:305–11.CrossRefPubMed Davis A, Dobson R, Kaninia S, Espasandin M, Berg A, Giovannoni G, et al. Change practice now! Using atraumatic needles to prevent post lumbar puncture headache. Eur J Neurol. 2014;21:305–11.CrossRefPubMed
19.
go back to reference Alcolea D, Martínez-Lage P, Izagirre A, Clerigué M, Carmona-Iragui M, Alvarez RM, et al. Feasibility of lumbar puncture in the study of cerebrospinal fluid biomarkers for Alzheimer's disease: a multicenter study in Spain. J Alzheimer's Dis. 2014;39:719–26. Alcolea D, Martínez-Lage P, Izagirre A, Clerigué M, Carmona-Iragui M, Alvarez RM, et al. Feasibility of lumbar puncture in the study of cerebrospinal fluid biomarkers for Alzheimer's disease: a multicenter study in Spain. J Alzheimer's Dis. 2014;39:719–26.
Metadata
Title
Alzheimer’s disease cerebrospinal fluid biomarkers are not influenced by gravity drip or aspiration extraction methodology
Authors
Alan Rembach
Lisbeth A. Evered
Qiao-Xin Li
Tabitha Nash
Lesley Vidaurre
Christopher J. Fowler
Kelly K. Pertile
Rebecca L. Rumble
Brett O. Trounson
Sarah Maher
Francis Mooney
Maree Farrow
Kevin Taddei
Stephanie Rainey-Smith
Simon M. Laws
S. Lance Macaulay
William Wilson
David G. Darby
Ralph N. Martins
David Ames
Steven Collins
Brendan Silbert
Colin L. Masters
James D. Doecke
the AIBL Research Group
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2015
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-015-0157-7

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