Affiliations: [a] Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, University of Antwerp, Antwerp, Belgium | [b] Biobank, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium | [c] Innogenetics NV (part of Fujirebio), Ghent, Belgium | [d] Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium
Correspondence:
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Correspondence to: Dr. Nathalie Le Bastard, University of Antwerp, Campus Drie Eiken, Building T Room 5.27, Universiteitsplein 1, 2610 Antwerp, Belgium. Tel.: +32 3 265 26 31; Fax: +32 3 265 26 18; E-mail: [email protected].
Note: [1] Present address: Now an employee of IDDI, Louvain-la-Neuve, Belgium.
Note: [2] Present address: Co-founders and employees of ADx Neurosciences, Ghent, Belgium.
Abstract: Combined analysis of the Alzheimer's disease (AD) biomarkers amyloid-β1-42 (Aβ1-42), total tau (T-tau), and hyperphosphorylated tau (P-tau181P) in cerebrospinal fluid (CSF) reduces the uncertainty associated with clinical dementia diagnosis. The present study evaluated the diagnostic accuracy of the CSF biomarker concentrations obtained with a multi-analyte Luminex assay (INNO-BIA AlzBio3) in comparison to single-analyte ELISA tests (INNOTEST). Data from 66 pathologically-confirmed dementia patients (51 AD and 15 non-AD) and 95 controls were included. Cut-off values were determined for each individual biomarker determined using both methods for different diagnostic challenges (dementia-controls; AD-controls; AD-non-AD). Comparing the diagnostic accuracy of individual cut-off values between INNO-BIA and INNOTEST, no relevant differences could be identified. Logistic regression was used in addition to identify the best combination of predictor variables (biomarkers). Discrimination of dementia patients from controls using Aβ1-42 and T-tau yielded a diagnostic accuracy of 0.87 and 0.90 for INNO-BIA and INNOTEST, respectively. Discriminating AD patients from controls, the diagnostic accuracy was 0.90 and 0.93 for INNO-BIA and INNOTEST, respectively. Optimal discrimination of AD and non-AD patients was achieved by combining Aβ1-42 and P-tau181P (diagnostic accuracy = 0.86). In conclusion, which AD biomarkers or combination thereof are most informative is dependent on the differential diagnosis, but the clinical value of these markers in each of the differential diagnoses is independent of the method by which concentrations are determined. Since the clinical value of the ELISA (INNOTEST) and Luminex (INNO-BIA) tests is comparable, further research to select the most suitable analytical platform for routine CSF biomarker measurements is needed.
