We measured apolipoprotein E (apoE) level in neutral and acidic pH extracts of the frontal, temporal and cerebellar cortices from patients with definite Alzheimer's disease (AD) and controls, and analyzed the relationship among apoE levels, clinical and neuropathological findings, and apoE genotype. Our data showed that the levels varied in different brain regions being lowest in the frontal cortex and highest in the cerebellum in Ad brains. ApoE levels in neutral pH extracts from the frontal cortex from AD patients were significantly lower than those of controls, and correlated negatively with the number of neurofibrillary tangles. ApoE genotype was not associated with the levels of apoE. There was no correlation between apoE levels and amyloid load or synaptophysin-immunoreactivity in the brain. We conclude that apoE levels are not increased in AD brains. However, apoE levels vary in different brain regions, and local factors related to the synthesis and metabolism of apoE may be crucial in the pathogenesis of AD.