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

Alzheimers Res Ther. 2015 Nov 19;7(1):71. doi: 10.1186/s13195-015-0157-7.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / genetics
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Apolipoprotein E4 / genetics
  • Biomarkers / cerebrospinal fluid
  • Cognitive Dysfunction / cerebrospinal fluid*
  • Cognitive Dysfunction / genetics
  • Cohort Studies
  • Female
  • Gravitation
  • Humans
  • Male
  • Mental Status Schedule
  • Paracentesis / instrumentation
  • Paracentesis / methods*
  • Peptide Fragments / cerebrospinal fluid
  • Phosphorylation
  • Psychometrics
  • Reproducibility of Results
  • Spinal Puncture / instrumentation
  • Spinal Puncture / methods*
  • Time Factors
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Apolipoprotein E4
  • Biomarkers
  • MAPT protein, human
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins