Validation of the AD-CSF-index in autopsy-confirmed Alzheimer's disease patients and healthy controls.
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.
Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Hanne
H
Struyfs
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Barcelona, Spain Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain Barcelona Beta Brain Research Centre, Fundació Pasqual Maragall, Barcelona, Spain.
José L
JL
Molinuevo
Biobank, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Jean-Jacques
JJ
Martin
Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium Biobank, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium Department of Neurology and Alzheimer Research Center, University Medical Center Groningen (UMCG), Groningen, The Netherlands.
Peter Paul
PP
De Deyn
Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.
Sebastiaan
S
Engelborghs
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D001344:Autopsy / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012372:ROC Curve; D012680:Sensitivity and Specificity; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D016875:tau Proteins
Alzheimer's disease; biomarkers; cerebrospinal fluid; diagnostic accuracy; sensitivity; specificity