ASSOCIATION OF APOLIPOPROTEIN-E WITH MURINE AMYLOID-A PROTEIN AMYLOID

BACKGROUND: Experimental amyloid A protein (AA) amyloidosis in mice is the most rapid type of amyloid formed, thus providing a valuable mode l to study amyloid formation. Recent studies have suggested the import ance of apolipoprotein E (apoE) in Alzheimer's disease and systemic am yloidoses. To help understand the role of apoE in amyloidoses, we exam ined amyloid tissue for the presence of apoE in mouse AA amyloid. EXPE RIMENTAL DESIGN: Mice were injected with amyloid-enhancing factor and silver nitrate to induce amyloid deposition. Spleens were examined for Congo red staining and serum amyloid A, serum amyloid P component, an d apoE immunostaining. In addition, RNA analysis was performed to meas ure the expression of apoE in various tissues after amyloid induction. RESULTS: We have found that apoE is associated with mouse amyloid. Ab to apoE consistently detected the presence of increased levels of apo E in amyloid tissue. Immunohistochemical analyses confirmed that the a poE immunoreactivity co-associated with AA and serum amyloid P in the amyloid fibrils. Northern blot analysis of amyloid tissue showed an in crease in apoE messenger RNA compared with control tissue. CONCLUSIONS : This is the first demonstration of apoE in mouse amyloid tissue. The data presented here, along with previous studies, suggest that apoE m ay be involved in amyloidogenesis. These studies validate the mouse mo del for studying the role of apoE in amyloid fibrillogenesis. The use of transgenic and gene-inactivated mice will help to elucidate the rol e and mechanism of apoE in amyloid formation.