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Updated: Aug 4, 2026

4D Imaging of Protein Aggregation in Live Cells
Published on: April 5, 2013
Altered localization of amyloid precursor protein under endoplasmic reticulum stress
Takashi Kudo1, Masayo Okumura, Kazunori Imaizumi
1Division of Psychiatry, Course of Internal Medicine, Osaka University Graduate School of Medicine, Osaka, Japan. kudo@psy.med.osaka-u.ac.jp
Abstract:
Recent reports have shown that the endoplasmic reticulum (ER) stress is relevant to the pathogenesis of Alzheimer disease. Following the amyloid cascade hypothesis, we therefore attempted to investigate the effects of ER stress on amyloid-beta peptide (Abeta) generation. In this study, we found that ER stress altered the localization of amyloid precursor protein (APP) from late compartments to early compartments of the secretory pathway, and decreased the level of Abeta 40 and Abeta 42 release by beta- and gamma-cutting. Transient transfection with BiP/GRP78 also caused a shift of APP and a reduction in Abeta secretion. It was revealed that the ER stress response facilitated binding of BiP/GRP78 to APP, thereby causing it to be retained in the early compartments apart from a location suitable for the cleavages of Abeta. These findings suggest that induction of BiP/GRP78 during ER stress may be one of the regulatory mechanisms of Abeta generation.
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