Hirano bodies accumulate C-terminal sequences of beta-amyloid precursor protein (beta-APP) epitopes.

Abstract

Hirano bodies (HB) are cytoplasmic inclusions predominantly found in the CA1 sector of the hippocampus. In Alzheimer's disease they are dislocated to the stratum pyramidale from their normal position in the stratum lacunosum. Hirano bodies are known to contain epitopes related to microfilaments (actin), neurofilaments, and microtubules (tau). In cryostat sections of the hippocampus from both Alzheimer's disease and normal patients, HB were decorated by two antisera raised against different sequences of the cytoplasmic domain of beta-amyloid precursor protein (beta-APP), and two antisera against the beta/A4 sequence of beta-APP, but not by two antisera directed against ectodomain (N-terminal) sequences of beta-APP. Thus, in contrast to dystrophic neurites in plaques, which are decorated by antibodies to either terminus of beta-APP, HB appear to be a site of preferential accumulation of C-terminal fragments of beta-APP, extending to include at least part of beta/A4.