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 model to study amyloid formation. Recent studies have suggested the importance of apolipoprotein E (apoE) in Alzheimer's disease and systemic amyloidoses. To help understand the role of apoE in amyloidoses, we examined amyloid tissue for the presence of apoE in mouse AA amyloid. EXPERIMENTAL
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, and apoE immunostaining. In addition, RNA analysis was performed to measure 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 apoE in amyloid tissue. Immunohistochemical analyses confirmed that the apoE immunoreactivity co-associated with AA and serum amyloid P in the amyloid fibrils. Northern blot analysis of amyloid tissue showed an increase 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 may be involved in amyloidogenesis. These studies validate the mouse model for studying the role of apoE in amyloid fibrillogenesis. The use of transgenic and gene-inactivated mice will help to elucidate the role and mechanism of apoE in amyloid formation.