Affiliations: [a] Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium | [b] Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Barcelona, Spain | [c] Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain | [d] Barcelona Beta Brain Research Centre, Fundació Pasqual Maragall, Barcelona, Spain | [e] Biobank, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium | [f] Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium | [g] Department of Neurology and Alzheimer Research Center, University Medical Center Groningen (UMCG), Groningen, The Netherlands
Correspondence:
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Correspondence to: Prof. Dr. S. Engelborghs, Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium. Tel.: +32 32652394; Fax: +32 32652618; E-mail: [email protected].
Abstract: The cerebrospinal fluid (CSF) biomarkers amyloid-β peptide of 42 amino acids (Aβ1-42), total tau-protein (T-tau), and tau phosphorylated at threonine 181 (P-tau181P) are used to diagnose Alzheimer's disease (AD). In order to increase diagnostic power, several biomarker combinations have been proposed. In that sense, a new CSF biomarker index was developed, the AD-CSF-index, which has been validated in clinically diagnosed AD patients using electrochemoluminescence based Meso Scale Discovery and single-analyte ELISA kits. This study validated the AD-CSF-index in neuropathologically diagnosed AD patients, using both single-analyte ELISA and multi-analyte Luminex assays. CSF of 51 neuropathologically diagnosed AD patients and of 95 controls was analyzed by commercially available single-analyte ELISA-kits (INNOTEST®, Innogenetics) and by a Research Use Only version of the multi-analyte Luminex xMAP® assay (INNO-BIA AlzBio3, Innogenetics). Subsequently the AD-CSF-indices were calculated. Both T-tau and P-tau181P AD-CSF-indices were significantly increased in AD patients when compared to controls (p < 0.001). The diagnostic power of the indices was calculated using ROC analyses, resulting in excellent sensitivity and specificity values that systematically exceeded the 80% threshold for discriminating autopsy-confirmed AD patients from controls, independent of the analytical platform. The power to discriminate between AD and non-AD dementias was not included in this study and should be validated in the future. In conclusion, this study validated the AD-CSF-index in autopsy-confirmed AD patients and has shown that its excellent diagnostic accuracy is independent of the analytical platform.
