Received on May 13, 2009
Accepted on September 17, 2009

Other Areas of Clinical Chemistry

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

¹ Department of Clinical Chemistry, VU University Medical Center, Alzheimer Center, Amsterdam, The Netherlands
² Department of Clinical Chemistry, and Department of Neurology, VU University Medical Center, Alzheimer Center, Amsterdam, The Netherlands
³ Department of Neurology, VU University Medical Center, Alzheimer Center, Amsterdam, The Netherlands

^* To whom correspondence should be addressed. E-mail: ma.blankenstein{at}vumc.nl.

BACKGROUND: To improve ante mortem diagnostic accuracy of Alzheimer disease (AD), measurement of the biomarkers amyloid-(1–42) (A42), total (Tau), and 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 A42, 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 A42; 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 A42; 375 (325–405) ng/L for Tau, and 52 (48–56) ng/L for pTau. Corresponding specificities were 83% (95% CI 76%–89%) for A42, 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 A42 = 373 + 0.82 x Tau. The area under the ROC curves of Tau and pTau showed significant fluctuation over time.

CONCLUSIONS: CSF biomarkers A42 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.