Neurobiology of Aging 27 (2006) 1202–1211 Cerebrospinal fluid tau and -amyloid in Alzheimer patients, disease controls and an age-matched random sample Bernd Ibach a,∗ , Harald Binder a , Margarethe Dragon a , Stefan Poljansky a , Ekkehard Haen a , Eberhard Schmitz b , Horst Koch a , Albert Putzhammer a , Hans Kluenemann a , Wolf Wieland c , Goeran Hajak a a Department of Psychiatry, Psychosomatics and Psychotherapy, Geriatric Psychiatry Research Group, University of Regensburg at the Bezirksklinikum, Universit¨ atsstraße 84, D-93053 Regensburg, Germany b Department of Anaesthesiology, Cartias Hospital St. Joseph, Landshuter Straße 65, 93053 Regensburg, Germany c Department of Urology, Cartias Hospital St. Joseph, Landshuter Straße 65, 93053 Regensburg, Germany Received 22 December 2004; received in revised form 15 June 2005; accepted 16 June 2005 Available online 8 August 2005 Abstract We prospectively evaluated the diagnostic accuracy of cerebrospinal fluid (CSF)--amyloid 1–42 (A 42 ), -total-tau (tau) and -phosphorylated- tau 181 (p-tau 181 ) as measured by sandwich ELISAs in the clinical routine of a community state hospital to discriminate between patients with Alzheimer’s disease (AD), healthy controls (HC), non-AD-dementias, a group composed of various psychiatric disorders (non-AD-dementias, mental diseases) and an age-matched random sample (RS) (total N = 219). By comparing patients with AD to HC as reference, tau revealed sensitivity (sens)/specificity (spec) of 88%/80%, p-tau 181 88%/80%, tau/A 42 -ratio 81%/85% and phospho-tau 181 /A 42 -ratio 81%/78%. Discriminative power between HC and all dementias under investigation was estimated lower for tau (78%/77%) and p-tau 181 (73%/79%). Relative to patients with AD, ROC analysis for the RS revealed highest sens/spec for p-tau 181 (79%/77%) and p-tau 181 /A 42 ratio (78%/75%). Differentiation between AD versus a group made of patients with various psychiatric disorders was optimised by using CSF-p-tau 181 (80%/77%). Under clinical routine conditions current CSF-biomarkers show a substantial capacity to discriminate between AD and HC as reference and to mark off AD patients from RS and heterogeneous diagnostic groups composed of non-AD dementias and other psychiatric conditions. Despite a residual substantial overlap between the groups, we conclude that current CSF markers are well suited to support AD-related diagnostic procedures in every-day clinics. © 2005 Elsevier Inc. All rights reserved. Keywords: Alzheimer’s disease; Non-Alzheimer dementias; Dementia; Psychiatric disorders; Depression; Schizophrenia; Cerebrospinal fluid; Tau; Phospho- rylated tau; -Amyloid 42 ; Random sample 1. Introduction Alzheimer’s disease (AD) is diagnosed extensively by clinical criteria [19,32]. In searching for optimized diagnoses [5,25], many studies reported elevated concentrations of tau- proteins and decreased levels of A 42 peptides in the cere- brospinal fluid (CSF) of patients with AD [1,2,6,8,10,27,30]. Only a few studies report no significant change or even ∗ Corresponding author. Tel.: +49 941 941 2063; fax: +49 941 941 2079. E-mail addresses: bernd.ibach@klinik.uni-regensburg.de, bernd.ibach@medbo.de (B. Ibach). an increase of CSF-A 42 levels in AD [14,21]. Previous research emphasizes CSF tau, p-tau 181,199,231 and A 42 or their ratios as biological markers to differentiate clinical AD from healthy controls and from other dementias [4,9,13,17]. Besides CSF-banks, the AD-consensus report [7] empha- sizes studies on brain banks, because neuropathological confirmation is defined as the gold standard for diagnosing AD. The validity of this approach has been challenged by a community-based clinico-neuropathological study, which showed that a substantial number of demented and non-demented elderly people exhibited Alzheimer’s-, Lewy body- and vascular pathology simultaneously [23]. Thus, a 0197-4580/$ – see front matter © 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.neurobiolaging.2005.06.005