Identification of an important potential confound in CSF AD studies: aliquot volume.
BACKGROUND
Cerebrospinal fluid (CSF) amyloid β1-42 (Aβ1-42), total tau (T-tau) and phosphorylated tau181 (P-tau) are finding increasing utility as biomarkers of Alzheimer's disease (AD). The purpose of this study was to determine whether measured CSF biomarker concentrations were affected by aliquot storage volume and whether addition of detergent-containing buffer mitigates any observed effects.


METHODS
AD and control CSF was distributed into polypropylene tubes in aliquots of different volumes (50-1500 μL). Aβ1-42, T-tau and P-tau were measured with and without addition of Tween 20 (0.05%).


RESULTS
Measured concentrations of Aβ1-42 increased two-fold with aliquot storage volume. A volume increase of 10 µL caused an Aβ1-42 increase of 0.95 pg/mL [95% confidence interval (CI) 0.36-1.50, p=0.02] in controls, and 0.60 pg/mL (CI 0.23-0.98 pg/mL, p=0.003) in AD samples. Following addition of Tween 20, the positive relationship between Aβ1-42 and aliquot volume disappeared. T-tau and P-tau were not significantly affected.


CONCLUSIONS
CSF aliquot storage volume has a significant impact on the measured concentration of Aβ1-42. The introduction of a buffer detergent at the initial aliquoting stage may be an effective solution to this problem.
Jamie
J
Toombs
Ross W
RW
Paterson
Michael P
MP
Lunn
Jenifer M
JM
Nicholas
Nick C
NC
Fox
Miles D
MD
Chapman
Jonathan M
JM
Schott
Henrik
H
Zetterberg
D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D016477:Artifacts; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002021:Buffers; D006801:Humans; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D013048:Specimen Handling / Q000379:methods* / Q000592:standards; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D002021:Buffers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins