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

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.

Evolution of Alzheimer's Disease Cerebrospinal Fluid Biomarkers in Early Parkinson's Disease

“…First, although this cohort represents a unique large-scale international coordinated multicenter effort to collect standardized longitudinal assessments, findings in this dataset from a research setting require replication in independent population-based cohorts to generalize findings. The Roche Elecsys platform has advantages of high precision (percent coefficient of variance [%CV] values <5%), linearity of dynamic range of measurements, [16][17][18][19] and standard operating procedures were used for harmonized methods of CSF collection across PPMI sites; we examined the effect of needle type used during the lumbar puncture (LP) procedure and found no significant association of needle type with any of our AD CSF biomarkers, similar to other recent work in AD, 49 providing further critical data to optimize large-scale multicenter biomarker efforts needed to establish CSF biomarkers for use in clinical practice. Although our predictive models were robust, the magnitude of change in our clinical and biomarker values were relatively modest, likely due to the early stage of disease and relative short duration of follow-up for longitudinal biomarker values that may take decades to show progression.…”

Rubidium and potassium levels are altered in Alzheimer’s disease brain and blood but not in cerebrospinal fluid

“…Cerebrospinal fluid was collected using the gravity drip method described by Rembach et al [22]. Patients underwent a lumbar puncture procedure following an overnight fast, and up to 8 mL of CSF was collected directly into a 15 mL polypropylene tube.…”

Elecsys CSF biomarker immunoassays demonstrate concordance with amyloid-PET imaging

“…The CSF collection protocol has been published previously [17,18] and is aligned with the Alzheimer's Biomarkers Standardization Initiative [19]. Following an overnight fast, CSF was collected in the morning by lumbar puncture using a Temena (Polymedic®, EU) spinal needle micro-tip (22/27G × 103 mm; CAT 21922-27).…”

“…Aβ-PET imaging was performed with four different radiotracers: 11 C-Pittsburgh compound B (PiB), 18 F-NAV4694 (NAV), 18 F-Flutemetamol (FLUTE) or 18 F-Florbetapir (FBP). Methodology for each tracer has been previously described [23].…”