Assessing the commutability of reference material formats for the harmonization of amyloid-β measurements.
BACKGROUND
The cerebrospinal fluid (CSF) amyloid-β (Aβ42) peptide is an important biomarker for Alzheimer's disease (AD). Variability in measured Aβ42 concentrations at different laboratories may be overcome by standardization and establishing traceability to a reference system. Candidate certified reference materials (CRMs) are validated herein for this purpose.


METHODS
Commutability of 16 candidate CRM formats was assessed across five CSF Aβ42 immunoassays and one mass spectrometry (MS) method in a set of 48 individual clinical CSF samples. Promising candidate CRM formats (neat CSF and CSF spiked with Aβ42) were identified and subjected to validation across eight (Elecsys, EUROIMMUN, IBL, INNO-BIA AlzBio3, INNOTEST, MSD, Simoa, and Saladax) immunoassays and the MS method in 32 individual CSF samples. Commutability was evaluated by Passing-Bablok regression and the candidate CRM termed commutable when found within the prediction interval (PI). The relative distance to the regression line was assessed.


RESULTS
The neat CSF candidate CRM format was commutable for almost all method comparisons, except for the Simoa/MSD, Simoa/MS and MS/IBL where it was found just outside the 95% PI. However, the neat CSF was found within 5% relative distance to the regression line for MS/IBL, between 5% and 10% for Simoa/MS and between 10% and 15% for Simoa/MSD comparisons.


CONCLUSIONS
The neat CSF candidate CRM format was commutable for 33 of 36 method comparisons, only one comparison more than expected given the 95% PI acceptance limit. We conclude that the neat CSF candidate CRM can be used for value assignment of the kit calibrators for the different Aβ42 methods.
Maria
M
Bjerke
Ulf
U
Andreasson
Julia
J
Kuhlmann
Erik
E
Portelius
Josef
J
Pannee
Piotr
P
Lewczuk
Robert M
RM
Umek
Eugeen
E
Vanmechelen
Hugo
H
Vanderstichele
Erik
E
Stoops
Jennifer
J
Lewis
Manu
M
Vandijck
Vesna
V
Kostanjevecki
Andreas
A
Jeromin
Salvatore J
SJ
Salamone
Oliver
O
Schmidt
Anja
A
Matzen
Kairat
K
Madin
Udo
U
Eichenlaub
Tobias
T
Bittner
Leslie M
LM
Shaw
Ingrid
I
Zegers
Henrik
H
Zetterberg
Kaj
K
Blennow
D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D006801:Humans; D007118:Immunoassay / Q000592:standards*; D057230:Limit of Detection; D012015:Reference Standards; D053719:Tandem Mass Spectrometry
D016229:Amyloid beta-Peptides; D015415:Biomarkers