It is suggested that tau protein level in cerebrospinal fluid (CSF) could be a useful diagnositic marker for AD. Using the sandwich enzyme-linked immunosorbent assay (InnoGenetics), tau protein level was measured with the CSF obtained by lumbar puncture from AD and other dementia patients. High tau protein level was observed with dementia patients diagnosed as AD, frontal lobe dementia, and corticobasal degeneration. When the cut-off value was set to the mean+ 2 S.D. of the control subjects, tau protein level can be used as a biological marker. To elucidate the mechanism of the higher tau protein level in CSF of dementia patients, tau protein level was measured with postmortem ventricular CSF and brain tissue from ten AD patients, six healthy and six non-AD neurological controls. All CSF samples showed more than ten fold higher tau protein level than those of the control CSF obtained by lumbar puncture. The higher tau level was observed irrespective of age, postmortem delay or mobidity. There was no significant correlation between tau protein level in CSF and in brain tissue homogenate. To rule out the regional difference of tau level between ventricle and lumbar site, it was measured in the same individual just after death. The results indicated tau protein level in CSF was rapidly increased in 3-5 hours postmortum period. Considering the significant increase of tau in postmortum CSF, it is speculated that the compartmentation of tau in brain tissue and CSF is relatively preserved in AD. The higher tau level in CSF of dementia patients is not accounted for by the incomplete compartmentation of tau protein between brain tissue and CSF.