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

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 scquences of the cytoplasmic domain of β-amyloid precursor protein (β-APP), and two antisera against the β/A₄ sequence of β-APP, but not by two antisera directed against ectodomain (N-terminal) sequences of β-APP. Thus, in contrast to dystrophic neuritcs in plaques, which are decorated by antibodies to either terminus of β-APP, HB appear to be a site of preferential accumulation of C-terminal fragments of β-APP, extending to include at least part of β/A₄.