To examine the effect of apolipoprotein E (ApoE) 4 on the progression of Alzheimer's disease (AD), the clinical course of 33 AD patients (17 cases with ApoE epsilon4 and 16 cases without ApoE epsilon4) was evaluated with the mini-mental state examination (MMSE) and cerebrospinal fluid (CSF) biological markers. The decline of MMSE scores to zero was shortened in the ApoE4 group. During a mean follow-up of 20 months, a significant increase of CSF tau levels was observed in the ApoE4 group. A lower level of CSF A beta1-42(43) was found in both the ApoE4 and non-ApoE4 groups than in age-matched normal controls. The ApoE epsilon4 allele accelerates the progression of dementia and increases the levels of CSF tau in AD patients.