APOLIPOPROTEIN-E ACCUMULATES WITH THE PROGRESSION OF A-BETA DEPOSITION IN TRANSGENIC MICE

To study the role of apolipoprotein E (apoE) in vivo in deposits of am yloid beta protein (A beta), a major component of senile plaque amyloi d in the brain of patients with Alzheimer disease. the transgenic mice were examined by apoE immunostaining. The mice were systemically over expressing signal peptide and 99 amino acid residues of the carboxy-te rminal fragment of human amyloid beta protein precursor (beta APP) und er control of the powerful cytomegalovirus enhancer/chicken beta-actin promotor. A beta deposits appeared at 4 months and increased with agi ng in the acinar cells of the transgenic pancreas. Similarly, apoE dep osits appeared in the pancreatic acinar cells at 4 months old. The num ber and size of apoE deposits increased with aging and correlated with the progression of A beta deposits. Interstitial macrophages labelled by apoE immunostaining appeared at 8 months after birth and their num ber increased with aging. On serial section of the pancreata of 24-mon th-old mice, approximately 70% of A beta deposits were labelled with t he apoE antiserum. ApoE was detected in the highly insoluble formic ac id fraction of the transgenic pancreas by an immunoblot study. The Nor thern blot study revealed no increase in synthesis of endogenous apoE mRNA. These findings indicate that apoE is closely related to progress ion of A beta deposits with aging and suggest that A beta deposition i n the transgenic pancreas is similar to that in the senile plaque of A lzheimer brains. Therefore, our experimental system using transgenic m ice will provide a useful tool to analyze the molecular mechanism of A beta deposition in association with apoE in vivo.