Risk of Alzheimer's disease biological misdiagnosis linked to cerebrospinal collection tubes.

Author(s): Perret-Liaudet A, Pelpel M, Tholance Y, Dumont B, Vanderstichele H, Zorzi W, Elmoualij B, Schraen S, Moreaud O, Gabelle A, Thouvenot E, Thomas-Anterion C, Touchon J, Krolak-Salmon P, Kovacs GG, Coudreuse A, Quadrio I, Lehmann S

Publication: J Alzheimers Dis, 2012, Vol. 31, Page 13-20

PubMed ID: 22495345 PubMed Review Paper? No

Purpose of Paper

Conclusion of Paper

Studies

1. Study Purpose

   The purpose of this study was to investigate the chemical composition of collection tubes as a source of pre-analytical variability of three biomarkers of AD in CSF (AB; total tau protein, hTau; p-Tau181P). CSF specimens (2 ml) were collected from 12 patients by lumbar puncture directly into 4 different commercial tubes made of either polypropylene (PP) (Sarstedt 10 ml, Becton Dickinson 15 ml) or polystyrene (PS) (Fisher Scientific hemolysis tube 5 ml, Becton Dickinson 14 ml). CSF specimens were then stored on ice, centrifuged, aliquoted, and stored at -80 degrees C for less than 6 months before analysis.

   Summary of Findings:

   AB40 and AB42 concentrations differed significantly among all four types of collection tubes examined (p<0.05), with the highest concentrations observed in CSF specimens collected into polypropylene tubes from Sarstedt followed by Fisher Scientific's hemolysis polystyrene were also present, with significantly lower concentrations among CSF specimens collected in polystyrene tubes from Becton Dickinson compared to either brand of polypropylene tubes. For p-Tau181P, significant differences in concentration was limited to CSF specimens collected into Fisher Scientific's hemolysis polystyrene tubes compared to other tube types (p<0.05). The authors note that the magnitude of variation attributable to tube type carries a potential risk for AD misdiagnosis for AB40 and AB42, but not other markers.

   Biospecimens

   • Bodily Fluid - Cerebrospinal Fluid

   Preservative Types

   • Frozen

   Diagnoses:

   • Alzheimer's Disease

   Platform:

   Analyte	Technology Platform
   Peptide	ELISA
   Protein	ELISA

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   ELISA Specific	Targeted peptide/protein	hTau p-Tau181P AB40 AB42
   Biospecimen Acquisition	Type of collection container/solution	Sarstedt 10 ml tube (PP) Becton Dickinson 15 ml tube (PP) Fisher Scientific hemolysis tube 5 ml (PS) Becton Dickinson 14 ml tube (PS)

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2. Study Purpose

   The purpose of this study was to assess potential differences in AD biomarkers levels in CSF stored in polypropylene collection tubes from different manufacturers for different lengths of time prior to analysis. CSF specimens from 6 patients were collected directly into Falcon 15 ml polypropylene tubes before centrifugation, aliquoting and storage in one of 11 commercial collection tubes for 15 min at room temperature or 24 hours at 2-8 degrees C prior to frozen storage at -80 degrees C. The chemical composition of each tube was verified by differential scanning calorimetry and Fourier Transformed Infrared spectroscopy. Tube composition consisted of polypropylene (PP), a polypropylene and polyethylene copolymer (PP-PE), or polypropylene, polyethylene and an unknown copolymer (PP-PE+Unknown).

   Summary of Findings:

   Significant differences in AB1-42, hTau, and pTau (p<0.05) levels were present between specimens stored in the different polypropylene-containing tubes Maximum median variations were highest for AB 1-42 (-48%/+31%), but within a range deemed acceptable by the authors for hTau (-8%/+8%) and p-Tau181P (-4%/+6%). Effects of storage tube type were present in specimens stored for 15 min or 24 h and significant differences were not present between the two timepoints. Artificially increasing protein content abolished tube-type effects over time, supporting the author's hypothesis of AD biomarker adsorption to the tube surface. The authors suggest that AD biomarker thresholds should be specific to collection tube type and handling protocols.

   Biospecimens

   • Bodily Fluid - Cerebrospinal Fluid

   Preservative Types

   • Frozen

   Diagnoses:

   • Alzheimer's Disease

   Platform:

   Analyte	Technology Platform
   Peptide	ELISA
   Protein	ELISA

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Biospecimen Acquisition	Type of collection container/solution	Greiner 15 ml tube (PP-PE) Deltalab 12 ml tube (PP-PE) Evergreen 30 ml tube(PP-PE) CML 15 ml tube (PP-PE) Sarstedt 10 ml tube (PP-PE, unknown copolymer) Falcon 14 ml tube (PP-PE) Nalgene 2 ml tube (PP-PE, unknown copolymer) Falcon 15 ml tube (PP-PE) Gosselin 5 ml tube (PP)
   ELISA Specific	Targeted peptide/protein	hTau p-Tau181P AB1-42
   Storage	Storage duration	15 min 24 h

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