Conversion of brain apolipoprotein E to an insoluble form in a mouse modelof Alzheimer disease

A beta deposition in the APP(V717F) transgenic model of Alzheimer's patholo gy 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 hip pocampus and colter of aged transgenic animals but were unchanged in wild t ype or young APP(V717F) animals. Soluble apoE levels were unaltered. A beta levels were also measured and a positive correlation between apoE and A be ta in the insoluble fraction was observed. ApoE transcription was increased similar to3-fold in the hippocampus of 17-month-old APP(V717F) mice, sugge sting a region-specific upregulation of apoE transcription in the brains of APP(V717F) mice to compensate for apoE sequestered with fibrillar A beta. NeuroReport 12:1265-1270 (C) 2001 Lippincott Williams & Wilkins.