Simultaneous measurement of beta-amyloid(1-42), total tau, and phosphorylated tau (Thr181) in cerebrospinal fluid by the xMAP technology.
BACKGROUND
To simultaneously study several biomarkers for Alzheimer disease (AD), we used the xMAP technology to develop and evaluate a multiparametric bead-based assay for quantification of beta-amyloid((1-42)) [Abeta((1-42))], total tau (T-TAU), and hyperphosphorylated tau [P-TAU((181P))] in cerebrospinal fluid (CSF).


METHODS
We compared the new multianalyte assay format with established ELISA techniques for the same proteins. We then performed a clinical study using CSF samples from patients with AD or mild cognitive impairment with progression to AD, healthy controls, and patients with other neurologic disorders.


RESULTS
The INNO-BIA AlzBio3 selectively and specifically measured Abeta((1-42)), T-TAU, and P-TAU((181P)) in the CSF. The new assay format had intra- and interassay CVs <10% for all analytes, even at low concentrations. The measurement range of the new assay was 3 to 4 logs compared with 1 to 2 logs for ELISAs. By plotting the mean of the values obtained in ELISA and the xMAP technology against the difference, we found that a correction factor could be used to convert xMAP results to ELISA values. The clinical study demonstrated that the new multiparametric assay could accurately distinguish patients with AD from patients with other neurologic disorders or control patients, with the diagnostic accuracy reaching recommended consensus criteria for specificity and sensitivity.


CONCLUSIONS
The new multiparametric method may be able to replace the corresponding ELISA methods.
Olsson
Annika
A
Institute of Clinical Neuroscience, Sahlgrenska University Hospital, Mölndal, Sweden. Annika.Olsson@neuro.gu.se
Vanderstichele
Hugo
H
Andreasen
Niels
N
De Meyer
Geert
G
Wallin
Anders
A
Holmberg
Björn
B
Rosengren
Lars
L
Vanmechelen
Eugeen
E
Blennow
Kaj
K
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D000911:Antibodies, Monoclonal; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003072:Cognition Disorders / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D012680:Sensitivity and Specificity; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins