Elevated levels of tau-protein in cerebrospinal fluid of patients with Creutzfeldt–Jakob disease Markus Otto a, *, Jens Wiltfang b , Hayrettin Tumani a , Inga Zerr a , Maria Lantsch a , Johannes Kornhuber b , Thomas Weber d , Hans A. Kretzschmar c , Sigrid Poser a a Department of Neurology, Georg-August-University Goettingen, D-37075 Goettingen, Germany b Department of Psychiatry, Georg-August-University Goettingen, D-37075 Goettingen, Germany c Department of Neuropathology, Georg-August-University Goettingen, D-37075 Goettingen, Germany d Department of Neurology, Marienkrankenhaus Hamburg, D-22087 Hamburg, Germany Received 21 February 1997; revised version received 7 March 1997; accepted 7 March 1997 Abstract Creutzfeldt–Jakob disease (CJD) is a rare, fatal, neurodegenerative disease caused by a transmissible agent designated as proteinaceous infectious agent (prion). Searching for biochemical markers of CJD, we analysed cerebrospinal fluid (CSF) samples of 53 patients for tau- protein using an enzyme linked immunoassay (ELISA). In a group of 21 patients with definite CJD seen in the German case control study for CJD, tau-protein concentrations in CSF were significantly higher than in two control-groups of patients with other diseases (median 13153 pg/ml, range 1533–27648 pg/ml; P = 0.0001). One control group comprised 19 patients who were seen in the same study and were diagnosed as having other dementing diseases (tau concentration: median 558 pg/ml, range 233–1769 pg/ml). The second control group comprised 13 patients from our hospital with no dementing disease (tau concentration: median 296 pg/ml, range 109–640 pg/ml). We conclude that determination of tau protein levels in CSF is a useful marker for laboratory diagnosis of CJD.  1997 Elsevier Science Ireland Ltd. Keywords: Creutzfeldt–Jakob disease; Tau-protein; Cerebrospinal fluid; ELISA; Dementia; Alzheimer’s disease Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and ultimately fatal disorder of the central nervous system belonging to the transmissible spongiform encephalopathies [3]. The transmissible agent has been termed proteinaceous infectious agent (prion) [11]. CJD occurs with an incidence of 0.5–1 cases per million population per year [1]. The clinical syndrome is characterised by a rapidly progressive dementia and a lethality of more than 90% within 1 year [3]. To date, a definite diagnosis can only be made by neuro- pathological examination and demonstration of the patho- logical isoform of the prion protein (PrP Sc ) in human brain tissue [8]. The main differential diagnosis of CJD in the early state of the disease is Alzheimer’s disease [19]. Tau- protein is the main constituent of the intracellular neurofi- brillary tangles in Alzheimer’s disease and cerebrospinal fluid (CSF) concentrations are reported to be elevated due to leakage in patients with Alzheimer’s disease [7,14]. Due to an overlap in pathogenic mechanisms in CJD and Alz- heimer’s disease [5], we examined the diagnostic potential of tau-protein in the CSF of CJD-patients. CSF samples of 53 patients were analysed for tau-protein concentration. Forty of these patients were recruited from the CSF-bank of the German Creutzfeldt–Jakob surveil- lance unit [16]. These patients were seen by at least one member of the Creutzfeldt–Jakob surveillance team. After lumbar puncture, CSF was immediately put on dry ice and then stored at -80°C. Patients with a rapidly progressive dementia of less than 2 years, periodic sharp wave complexes (PSWCs) in EEG recordings, and two of the following four findings: (1) myo- clonus; (2) visual and/or cerebellar symptoms; (3) pyrami- dal and/or extrapyramidal tract signs; and (4) akinetic mutism, were classified as ‘probable’. Those fulfilling the Neuroscience Letters 225 (1997) 210–212 0304-3940/97/$17.00  1997 Elsevier Science Ireland Ltd. All rights reserved PII S0304-3940(97)00215-2 * Corresponding author. Tel.: +49 551 396636; fax: +49 551 397020; e-mail: 100634.133@compuserve.com