Diagnostic performance of a CSF-biomarker panel in autopsy-confirmed dementia.
To establish diagnostic performance of the cerebrospinal fluid (CSF) biomarkers beta-amyloid peptide (Abeta(1-42)), total tau-protein (T-tau) and tau phosphorylated at threonine 181 (P-tau(181P)) compared to clinical diagnosis, biomarker levels were determined in CSF samples from 100 autopsy-confirmed dementia and 100 control subjects. As the control and dementia groups were not age-matched and given the significant associations of biomarker concentrations with age in controls, age-corrected biomarker concentrations were calculated. New models were constructed by means of logistic regression. Using all biomarkers, dementia could be discriminated from controls (sensitivity (S)=86%, specificity (Sp)=89%). T-tau and Abeta(1-42) optimally discriminated Alzheimer's disease (AD) from other dementias (NONAD) and controls (S=90%, Sp=89%). AD was optimally discriminated from NONAD using P-tau(181P) and Abeta(1-42) (S=80%, Sp=93%). Diagnostic accuracy of the latter model (82.7%) was comparable to clinical diagnostic accuracy (81.6%) that was based on a whole clinical work-up (including imaging). Using this model, in cases with clinically doubtful diagnoses, a correct diagnosis would have been established in 4/6 autopsy-confirmed AD and 3/3 autopsy-confirmed NONAD cases. The value of biomarkers in differential dementia diagnosis was shown, using pathological diagnosis as a reference. New models have been developed, achieving sensitivity, specificity and diagnostic accuracy levels, consistently exceeding 80%.
Engelborghs
Sebastiaan
S
Department of Neurology and Memory Clinic, Middelheim General Hospital (ZNA), Lindendreef 1, 2020 Antwerp, Belgium.
De Vreese
Karen
K
Van de Casteele
Tom
T
Vanderstichele
Hugo
H
Van Everbroeck
Bart
B
Cras
Patrick
P
Martin
Jean-Jacques
JJ
Vanmechelen
Eugeen
E
De Deyn
Peter Paul
PP
D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D001344:Autopsy; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003704:Dementia / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D003936:Diagnosis, Computer-Assisted / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins