Lysosomal generation of amyloid β protein species in transgenic mice

Abstract

Soluble amyloid β protein (A β)1–40 and highly amyloidogenic A β1–42/43 were immunocytochemically labeled in lysosomes of acinar cells and macrophages in the pancreas of transgenic mice systemically expressing a C-terminal fragment of the A β precursor. A β1–42/43 and long A β species extending their C-termini were detected in the detergent-insoluble fraction. Immunoreactivity of cathepsin D was markedly increased in lysosomes filled with A β fibrils. These findings indicated that A β1–40, A β1–42, A β1–43 and longer A β species were generated in the lysosomes of the transgenic pancreas, and suggested that the activation of cathepsin D, a candidate γ-secretase, leads to acceleration of A β amyloid formation.