We quantified microtubule-associated protein tau in CSF (CSF tau) using ELISA assay in 168 subjects: 81 patients with clinically diagnosed early Alzheimer's disease (AD), 43 patients with other dementia, 11 Down's syndrome patients, and 33 nondemented neurologic control subjects. Multivariate ANOVA showed an effect of diagnostic group (p < 0.01) and apolipoprotein E (apoE) allele (p < 0.005) on CSF tau. Comparison between diagnostic groups showed higher CSF tau levels in AD than in the control group (p < 0.001). However, CSF tau values in the non-AD dementia group did not differ significantly from those of AD patients or neurologic control subjects. Tau levels were increased (p < 0.005) in AD patients with apolipoprotein E epsilon4 allele, a well-characterized risk factor of AD, compared with AD patients without epsilon4 allele, and the highest values were found in AD patients with two epsilon4 alleles. These increased levels of CSF tau may indicate pronounced neuronal degeneration and neurofibrillar pathology at the early stage of AD in patients carrying the epsilon4 allele. This study shows that the current ELISA test for CSF tau is not sensitive and specific enough to distinguish early AD from other dementias and indicates that in the interpretation of CSF tau analysis as a diagnostic tool, the apoE genotype should also be taken into account.