Accuracy of cerebrospinal fluid Aβ1-42 measurements: evaluation of pre-analytical factors using a novel Elecsys immunosassay.
BACKGROUND
A decreased level of Aβ1-42 in cerebrospinal fluid (CSF) is characteristic of Alzheimer disease and often used to support clinical diagnosis. The measured concentration of CSF Aβ1-42, however, depends strongly on several pre-analytical and analytical "confounding" factors such as sample collection, material of testing tube, CSF handling and storage procedures (e.g. transfer to new tubes after centrifugation, freeze-thaw effects). As a consequence, substantial variations in the measured levels of this biomarker are observed even for the same sample. This study investigates whether the accuracy of quantitative analysis of CSF Aβ1-42 can be improved by pre-analytical treatment of CSF with agents that could potentially reduce a freeze-thaw and adhesion-related depletion of Aβ1-42 from CSF, including modulators of Aβ aggregation and cryoprotecting or anti-adhesion agents.


METHODS
The concentration of CSF Aβ1-42 was assessed with a novel Elecsys immunoassay developed for quantification of Aβ1-42 in human CSF.


RESULTS
Low-molecular weight Aβ oligomerization inhibitors, β-sheet breaker peptides, or the mid domain 4G8 antibody do not improve the stability of CSF Aβ1-42 during a repeated freeze-thaw treatment. Cryoprotecting agents reduce a freeze-thaw dependent loss of Aβ1-42 only when spiked to CSF to final concentration of 300 mM or higher. Adhesion of Aβ1-42 can be prevented by pre-treating CSF with Tween or by using tubes with a siliconized surface.


CONCLUSIONS
Between-center variability in measured level of CSF Aβ1-42 can be reduced only by standardized CSF collection into one specific tube that, without centrifugation, transfer or other types of pre-analytical processing, is directly analyzed after sample collection.
.
Malgorzata
http://orcid.org/0000-0001-9857-6320
M
Rozga
.
Tobias
T
Bittner
.
Kina
K
Höglund
.
Kaj
K
Blennow
D000544:Alzheimer Disease / Q000175:diagnosis; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid* / Q000276:immunology; D000906:Antibodies / Q000276:immunology; D003451:Cryoprotective Agents / Q000737:chemistry; D005615:Freezing; D006801:Humans; D007118:Immunoassay / Q000295:instrumentation / Q000379:methods*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid* / Q000276:immunology; D011136:Polysorbates / Q000737:chemistry; D055550:Protein Stability; D013654:Taurine / Q000031:analogs & derivatives / Q000737:chemistry
D016229:Amyloid beta-Peptides; D000906:Antibodies; D003451:Cryoprotective Agents; D010446:Peptide Fragments; D011136:Polysorbates; C075222:amyloid beta-protein (1-42); D013654:Taurine; C001355:tramiprosate
Alzheimer disease; Aβ-peptide; Elecsys β-amyloid (1-42) assay; cerebrospinal fluid