The concentration of tau protein is elevated in the cerebrospinal fluid (CSF) in Alzheimer's disease (AD), suggesting that CSF tau may be a useful biochemical diagnostic marker for this disorder. We investigated CSF tau concentrations on two occasions in AD (n = 18), mild cognitive impairment (MCI, n = 9) and other dementing disease (OD, n = 9) by ELISA (Innotest hTau Antigen, Innogenetics, Belgium). Tau levels were statistically significant higher in the AD group than in MCI and OD groups on both occasions. Twelve of the AD patients showed increasing values of tau at follow-up and six demonstrated diminished values. All AD patients with increasing tau were carriers of one or two epsilon 4 alleles of the apolipoprotein E (APOE, gene. Of those AD cases with decreasing tau levels only three individuals had the epsilon 4 allele, a difference that was statistically significant (P < 0.05). These findings suggest that there may be apolipoprotein E (apoE) isoform-specific differences of tau regulation in AD.