Phosphorylated tau in human cerebrospinal fluid is a diagnostic marker forAlzheimer's disease

Microtubule-associated protein tau in cerebrospinal fluid (CSF) has been pr oposed as a diagnostic marker for Alzheimer's disease (AD), but there is ov erlap between AD patients and non-AD controls. To improve the diagnostic ac curacy, we measured phosphorylated tau in CSF, because phosphorylated tau a ccumulates as pathological paired helical filaments in neurons of the AD br ain. Immunoblot showed that CSF contained a 32 kDa N-terminal fragment of t au that was partially phosphorylated on Ser199, Thr231 and Ser235. A sandwi ch enzyme immunoassay revealed that phosphorylated CSF-tau levels were sign ificantly higher in AD patients than those in non-AD controls. Discriminati on between the two groups was clearer in phosphorylated CSF-tau than in tot al CSF-tau. The data indicate that elevated phosphorylated CSF-tau level is a more specific diagnostic marker for AD. (C) 1999 Elsevier Science Irelan d Ltd. All rights reserved.