Cerebrospinal fluid (CSF) total tau protein (tauT) is increased in Alzheimer's disease (AD) and may be of some help in the diagnostic work-up of demented patients. The aim of the present study was to investigate the diagnostic aid and the additional help (over that of clinical criteria) of tauT in different clinical situations. Double-sandwich enzyme-linked immunosorbent assay was used to quantify tauT in 61 healthy controls and 241 patients with various neuropsychiatric diseases. Our results suggest that CSF tauT offers significant additional information over that of clinical criteria of AD, for the discrimination of AD from normal aging, depression, synucleinopathy, and possibly vascular dementia. However, for the differential diagnosis from frontotemporal dementia, corticobasal ganglionic degeneration, and secondary dementia, the diagnostic value is inadequate.