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

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

doi:10.1186/s13195-015-0157-7

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

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 AmesSteven Collins, Brendan Silbert, Colin L. Masters, James D. Doecke, The AIBL Research Group

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Article number	71
Pages (from-to)	1-8
Number of pages	8
Journal	Alzheimer's Research and Therapy
Volume	7
DOIs	https://doi.org/10.1186/s13195-015-0157-7
Publication status	Published - 19 Nov 2015
Externally published	Yes

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Copyright the Author(s) 2015. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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Rembach, A., Evered, L. A., Li, Q. X., Nash, T., Vidaurre, L., Fowler, C. J., Pertile, K. K., Rumble, R. L., Trounson, B. O., Maher, S., Mooney, F., Farrow, M., Taddei, K., Rainey-Smith, S., Laws, S. M., Macaulay, S. L., Wilson, W., Darby, D. G., Martins, R. N., ... The AIBL Research Group (2015). Alzheimer's disease cerebrospinal fluid biomarkers are not influenced by gravity drip or aspiration extraction methodology. Alzheimer's Research and Therapy, 7, 1-8. [71]. https://doi.org/10.1186/s13195-015-0157-7

Rembach, Alan ; Evered, Lisbeth A. ; Li, Qiao Xin ; Nash, Tabitha ; Vidaurre, Lesley ; Fowler, Christopher J. ; Pertile, Kelly K. ; Rumble, Rebecca L. ; Trounson, Brett O. ; Maher, Sarah ; Mooney, Francis ; Farrow, Maree ; Taddei, Kevin ; Rainey-Smith, Stephanie ; Laws, Simon M. ; Macaulay, S. Lance ; Wilson, William ; Darby, David G. ; Martins, Ralph N. ; Ames, David ; Collins, Steven ; Silbert, Brendan ; Masters, Colin L. ; Doecke, James D. ; The AIBL Research Group. / Alzheimer's disease cerebrospinal fluid biomarkers are not influenced by gravity drip or aspiration extraction methodology. In: Alzheimer's Research and Therapy. 2015 ; Vol. 7. pp. 1-8.

@article{ac358161a2944925af12dc20b6fbd352,

title = "Alzheimer's disease cerebrospinal fluid biomarkers are not influenced by gravity drip or aspiration extraction methodology",

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.",

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

note = "Copyright the Author(s) 2015. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2015",

month = nov,

day = "19",

doi = "10.1186/s13195-015-0157-7",

language = "English",

volume = "7",

pages = "1--8",

journal = "Alzheimer's Research and Therapy",

issn = "1758-9193",

publisher = "Springer, Springer Nature",

}

Rembach, A, Evered, LA, Li, QX, Nash, T, Vidaurre, L, Fowler, CJ, Pertile, KK, Rumble, RL, Trounson, BO, Maher, S, Mooney, F, Farrow, M, Taddei, K, Rainey-Smith, S, Laws, SM, Macaulay, SL, Wilson, W, Darby, DG, Martins, RN, Ames, D, Collins, S, Silbert, B, Masters, CL, Doecke, JD & The AIBL Research Group 2015, 'Alzheimer's disease cerebrospinal fluid biomarkers are not influenced by gravity drip or aspiration extraction methodology', Alzheimer's Research and Therapy, vol. 7, 71, pp. 1-8. https://doi.org/10.1186/s13195-015-0157-7

Alzheimer's disease cerebrospinal fluid biomarkers are not influenced by gravity drip or aspiration extraction methodology. / Rembach, Alan; Evered, Lisbeth A.; Li, Qiao Xin; Nash, Tabitha; Vidaurre, Lesley; Fowler, Christopher J.; Pertile, Kelly K.; Rumble, Rebecca L.; Trounson, Brett O.; Maher, Sarah; Mooney, Francis; Farrow, Maree; Taddei, Kevin; Rainey-Smith, Stephanie; Laws, Simon M.; Macaulay, S. Lance; Wilson, William; Darby, David G.; Martins, Ralph N.; Ames, David; Collins, Steven; Silbert, Brendan; Masters, Colin L.; Doecke, James D.; The AIBL Research Group.

In: Alzheimer's Research and Therapy, Vol. 7, 71, 19.11.2015, p. 1-8.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Alzheimer's disease cerebrospinal fluid biomarkers are not influenced by gravity drip or aspiration extraction methodology

AU - Rembach, Alan

AU - Evered, Lisbeth A.

AU - Li, Qiao Xin

AU - Nash, Tabitha

AU - Vidaurre, Lesley

AU - Fowler, Christopher J.

AU - Pertile, Kelly K.

AU - Rumble, Rebecca L.

AU - Trounson, Brett O.

AU - Maher, Sarah

AU - Mooney, Francis

AU - Farrow, Maree

AU - Taddei, Kevin

AU - Rainey-Smith, Stephanie

AU - Laws, Simon M.

AU - Macaulay, S. Lance

AU - Wilson, William

AU - Darby, David G.

AU - Martins, Ralph N.

AU - Ames, David

AU - Collins, Steven

AU - Silbert, Brendan

AU - Masters, Colin L.

AU - Doecke, James D.

AU - The AIBL Research Group

N1 - Copyright the Author(s) 2015. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2015/11/19

Y1 - 2015/11/19

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84947249970&partnerID=8YFLogxK

U2 - 10.1186/s13195-015-0157-7

DO - 10.1186/s13195-015-0157-7

M3 - Article

C2 - 26581886

AN - SCOPUS:84947249970

VL - 7

SP - 1

EP - 8

JO - Alzheimer's Research and Therapy

JF - Alzheimer's Research and Therapy

SN - 1758-9193

M1 - 71

ER -

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

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