title: Alzheimer's disease cerebrospinal fluid biomarkers are not influenced by gravity drip or aspiration extraction methodology.
abstract: BACKGROUND
  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.
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria, 3010, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Rembach
authors.affiliation: Centre for Anaesthesia and Cognitive Function, Department of Anaesthesia and Perioperative Pain Medicine, St Vincent's Hospital, Melbourne, Australia. lis.evered@svha.org.au.
authors.forename: Lisbeth A
authors.initials: LA
authors.lastname: Evered
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria, 3010, Australia. q.li@unimelb.edu.au.
authors.forename: Qiao-Xin
authors.initials: QX
authors.lastname: Li
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria, 3010, Australia. tabitha.nash@florey.edu.au.
authors.forename: Tabitha
authors.initials: T
authors.lastname: Nash
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria, 3010, Australia. lesley.vidaurre@florey.edu.au.
authors.forename: Lesley
authors.initials: L
authors.lastname: Vidaurre
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria, 3010, Australia. christopher.fowler@florey.edu.au.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Fowler
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria, 3010, Australia. kelly.pertile@florey.edu.au.
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Pertile
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria, 3010, Australia. rebecca.rumble@florey.edu.au.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Rumble
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria, 3010, Australia. btrounson@unimelb.edu.au.
authors.forename: Brett O
authors.initials: BO
authors.lastname: Trounson
authors.affiliation: Centre for Anaesthesia and Cognitive Function, Department of Anaesthesia and Perioperative Pain Medicine, St Vincent's Hospital, Melbourne, Australia. sarah.maher@svhm.org.au.
authors.forename: Sarah
authors.initials: S
authors.lastname: Maher
authors.affiliation: Centre for Anaesthesia and Cognitive Function, Department of Anaesthesia and Perioperative Pain Medicine, St Vincent's Hospital, Melbourne, Australia. francis.mooney@svhm.org.au.
authors.forename: Francis
authors.initials: F
authors.lastname: Mooney
authors.affiliation: Alzheimer's Australia Victoria, 155 Oak Street, Parkville, Victoria, 3052, Australia. dr.maree.farrow@alzheimers.org.au.
authors.forename: Maree
authors.initials: M
authors.lastname: Farrow
authors.affiliation: Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia. k.taddei@ecu.edu.au.|Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, Western Australia, Australia. k.taddei@ecu.edu.au.
authors.forename: Kevin
authors.initials: K
authors.lastname: Taddei
authors.affiliation: Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia. s.rainey-smith@ecu.edu.au.|Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, Western Australia, Australia. s.rainey-smith@ecu.edu.au.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Rainey-Smith
authors.affiliation: Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia. s.laws@ecu.edu.au.|Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, Western Australia, Australia. s.laws@ecu.edu.au.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Laws
authors.affiliation: CSIRO Preventative Health Flagship, Parkville, Victoria, 3010, Australia. lance.macaulay@csiro.au.
authors.forename: S Lance
authors.initials: SL
authors.lastname: Macaulay
authors.affiliation: CSIRO Computational Informatics/Australian e-Health Research Centre, Brisbane, Queensland, 4029, Australia. bill.wilson@csiro.au.
authors.forename: William
authors.initials: W
authors.lastname: Wilson
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria, 3010, Australia. ddarby@unimelb.edu.au.
authors.forename: David G
authors.initials: DG
authors.lastname: Darby
authors.affiliation: Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia. r.martins@ecu.edu.au.|Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, Western Australia, Australia. r.martins@ecu.edu.au.
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
authors.affiliation: National Ageing Research Institute, Parkville, Victoria, 3050, Australia. dames@unimelb.edu.au.
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.affiliation: Department of Pathology, University of Melbourne, Parkville, 3010, Australia. s.collins@unimelb.edu.au.
authors.forename: Steven
authors.initials: S
authors.lastname: Collins
authors.affiliation: Centre for Anaesthesia and Cognitive Function, Department of Anaesthesia and Perioperative Pain Medicine, St Vincent's Hospital, Melbourne, Australia. brendan.silbert@svhm.org.au.
authors.forename: Brendan
authors.initials: B
authors.lastname: Silbert
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria, 3010, Australia. c.masters@unimelb.edu.au.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.affiliation: CSIRO Preventative Health Flagship, Parkville, Victoria, 3010, Australia. james.doecke@csiro.au.|CSIRO Computational Informatics/Australian e-Health Research Centre, Brisbane, Queensland, 4029, Australia. james.doecke@csiro.au.
authors.forename: James D
authors.initials: JD
authors.lastname: Doecke
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D006112:Gravitation; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D019152:Paracentesis / Q000295:instrumentation / Q000379:methods*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D011594:Psychometrics; D015203:Reproducibility of Results; D013129:Spinal Puncture / Q000295:instrumentation / Q000379:methods*; D013997:Time Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins