Clinical Chemistry 56: 248-253, 2010. First published October 15, 2009; 10.1373/clinchem.2009.130518
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Right arrow Proteomics and Protein Markers
(Clinical Chemistry. 2010;56:248-253.)
© 2010 American Association for Clinical Chemistry, Inc.

Proteomics and Protein Markers

Amyloid-β(1–42), Total Tau, and Phosphorylated Tau as Cerebrospinal Fluid Biomarkers for the Diagnosis of Alzheimer Disease

Cees Mulder1, Nicolaas A. Verwey1,2, Wiesje M. van der Flier2, Femke H. Bouwman2, Astrid Kok1, Evert J. van Elk1, Philip Scheltens2 and Marinus A. Blankenstein1,a

1 Department of Clinical Chemistry and 2 Department of Neurology, VU University Medical Center, Alzheimer Center, Amsterdam, the Netherlands.

aAddress correspondence to this author at: Department of Clinical Chemistry, VU University Medical Center, PO Box 7057, 1007MB Amsterdam, the Netherlands. Fax +31-20-4443895; e-mail ma.blankenstein{at}vumc.nl.

Background: To improve ante mortem diagnostic accuracy of Alzheimer disease (AD), measurement of the biomarkers amyloid-β(1–42) (Aβ42), total tau (Tau), and tau phosphorylated at threonine181 (pTau) in cerebrospinal fluid (CSF) has been proposed. We have used these markers and evaluated their performance.

Methods: From January 2001 to January 2007, we assessed Aβ42, Tau, and pTau by commercial ELISAs in CSF from 248 consecutive AD patients and 131 patients with subjective memory complaints attending our outpatient memory clinic. Diagnoses were made blind to the results of the biomarker assays. We assessed sensitivity and specificity and analyzed trends over time.

Results: Interassay CVs from analysis of pools of surplus CSF specimens were mean 11.3% (SD 4.9%) for Aβ42; 9.3% (1.5%) for Tau, and 9.4% (2.5%) for pTau, respectively (n = 7–18). To achieve 85% sensitivity, cutoff values were 550 (95% CI 531–570) ng/L for Aβ42; 375 (325–405) ng/L for Tau, and 52 (48–56) ng/L for pTau. Corresponding specificities were 83% (95% CI 76%–89%) for Aβ42, 78% (70%–85%) for Tau, and 68% (60%–77%) for pTau. Logistic regression to investigate the simultaneous impact of the 3 CSF biomarkers on the diagnosis yielded a sensitivity of 93.5% and specificity of 82.7%, at a discrimination line of Aβ42 = 373 + 0.82 x Tau. The area under the ROC curves of Tau and pTau showed significant fluctuation over time.

Conclusions: CSF biomarkers Aβ42 and Tau can be used as a diagnostic aid in AD. pTau did not have additional value over these 2 markers. Cutoff values, sensitivities, specificities, and discrimination lines depend on the patient groups studied and laboratory experience.




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