Aβ deposition in the APPv717F transgenic model of Alzheimer's pathology involves apolipoprotein E (apoE). We measured soluble and insoluble apoE in brain region extracts at an early and late stage of plaque development. The apoE levels in the insoluble fraction were greatly elevated in the hippocampus and cortex of aged transgenic animals but were unchanged in wild type or young APPv717F animals. Soluble apoE levels were unaltered. Aβ levels were also measured and a positive correlation between apoE and Aβ in the insoluble fraction was observed. ApoE transcription was increased ∼3-fold in the hippocampus of 17-month-old APPv717F mice, suggesting a region-specific upregulation of apoE transcription in the brains V717F of APP mice to compensate for apoE sequestered with fibrillar Aβ.