Immunohistochemical localization of amyloid β-protein with amino-terminal aspartate in the cerebral cortex of patients with Alzheimer's disease

Abstract

We investigated immunohistochemically the localization of amyloid β-protein (Aβ) with amino-terminal aspartate (N1[D]) in brains of patients with Alzheimer's disease, diffuse Lewy body disease and Down's syndrome. A monoclonal antibody, 4G8, which recognizes the middle portion of Aβ, was used as a reference antibody to label the total Aβ deposits. Double staining with anti-Aβ(N1[D]) and 4G8 revealed that Aβ deposits in the subiculum and the neocortical deep layers often lacked N1[D] immunoreactivity, indicating N-terminal truncation of Aβ in these deposits. Aβ deposits in the neocortical superficial layers and the presubicular parvopyramidal layer always contained Aβ with N1[D]. Such regional as well as laminar differences in the distribution of Aβ beginning at N1[D] suggest that some local factors influence N-terminal processing of Aβ deposited in the brain.