Back to Search
Start Over
An isogenic panel of App knock-in mouse models: Profiling β-secretase inhibition and endosomal abnormalities
- Source :
- Science Advances. 8
- Publication Year :
- 2022
- Publisher :
- American Association for the Advancement of Science (AAAS), 2022.
-
Abstract
- We previously developed single App knock-in mouse models of Alzheimer’s disease (AD) that harbor the Swedish and Beyreuther/Iberian mutations with or without the Arctic mutation ( App NL-G-F and App NL-F mice). We have now generated App knock-in mice devoid of the Swedish mutations ( App G-F mice) and evaluated its characteristics. Amyloid β peptide (Aβ) pathology was exhibited by App G-F mice from 6 to 8 months of age and was accompanied by neuroinflammation. Aβ-secretase inhibitor, verubecestat, attenuated Aβ production in App G-F mice, but not in App NL-G-F mice, indicating that the App G-F mice are more suitable for preclinical studies of β-secretase inhibition given that most patients with AD do not carry the Swedish mutations. Comparison of isogenic App knock-in lines revealed that multiple factors, including elevated C-terminal fragment β (CTF-β) and humanization of Aβ might influence endosomal alterations in vivo. Thus, experimental comparisons between different isogenic App , knock-in mouse lines will provide previously unidentified insights into our understanding of the etiology of AD.
- Subjects :
- Multidisciplinary
Subjects
Details
- ISSN :
- 23752548
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Science Advances
- Accession number :
- edsair.doi...........07fa8043c2e80015ca1734038a06394a
- Full Text :
- https://doi.org/10.1126/sciadv.abm6155