BPB Reports

Paper Details

BPB Reports
Vol. 7 No. 2 p.44-50 2024
Regular Article
Increased Expression of C/EBP Homologous Protein, a Marker of Endoplasmic Reticulum Stress, in the Brains of AppNL-G-F/NL-G-F Knock-in Alzheimer’s Disease Model Mice
  • Hiroaki Takemoto (Department of Molecular Toxicology, Faculty of Pharmaceutical Sciences, Toho University / hiroaki.takemoto@phar.toho-u.ac.jp)
Wei Dai 1) , Kotaro Ishibashi 1) , Hiroaki Takemoto 1) , Saki Ito 1) , Hikaru Kasuya 1) , Tadaaki Sato 2) , Takashi Saito 3) 4) , Takaomi C. Saido 4) , Kiyomitsu Nemoto 1)
1) Department of Molecular Toxicology, Faculty of Pharmaceutical Sciences, Toho University , 2) Department of Pharmaceutical Sciences, International University of Health and Welfare , 3) Department of Neurocognitive Science, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences , 4) Laboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science
Received: February 20, 2024;   Accepted: February 26, 2024;   Released: March 27, 2024
Keywords: Alzheimer’s disease, amyloid-β, C/EBP homologous protein, AppNL-G-F/NL-G-F

Alzheimer’s disease (AD) is one of the most common types of progressive dementia. Recently, endoplasmic reticulum (ER) stress was suggested as a potential event involved in AD development. Thus, targeting ER stress may be an effective AD treatment. The involvement of ER stress in the brains of amyloid precursor protein knock-in AD model mice (AppNL-G-F/NL-G-F) with Swedish/Iberian/Arctic mutations found in human familial AD remains unclear. This study aimed to clarify whether the expression of ER stress marker C/EBP homologous protein (CHOP) was enhanced in the brains of AppNL-G-F/NL-G-F AD model mice. Our immunofluorescence staining results showed that similar to the expression pattern of amyloid-β (Aβ), CHOP demonstrated an age-dependent increase in the numbers and sizes of spotted signals in the cerebral cortex and hippocampus of these 4- to 10-month-old AD model mice but not in their age-matched controls. These findings suggested that CHOP expression was upregulated in close association with Aβ expression, and that CHOP was involved in neuropathy caused by Aβ accumulation. Future investigations of the localization and variations in expression levels of other ER stress-related proteins in this mouse model using immunofluorescence staining will lead to a more detailed estimation of the relationship between ER stress and AD pathogenesis.