Longitudinal characterization reveals behavioral impairments in aged APP knock in mouse models
Abstract APP knock-in (KI) mice serve as an exciting new model system to understand amyloid beta (Aβ) pathology, overcoming many of the limitations of previous overexpression-based model systems. The APPSAA mouse model (containing the humanized APP with three familial Alzheimer’s disease mutations)...
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| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-89051-8 |
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| author | Lisa Blackmer-Raynolds Lyndsey D. Lipson Isabel Fraccaroli Ian N. Krout Jianjun Chang Timothy Robert Sampson |
| author_facet | Lisa Blackmer-Raynolds Lyndsey D. Lipson Isabel Fraccaroli Ian N. Krout Jianjun Chang Timothy Robert Sampson |
| author_sort | Lisa Blackmer-Raynolds |
| collection | DOAJ |
| description | Abstract APP knock-in (KI) mice serve as an exciting new model system to understand amyloid beta (Aβ) pathology, overcoming many of the limitations of previous overexpression-based model systems. The APPSAA mouse model (containing the humanized APP with three familial Alzheimer’s disease mutations) and the APPWT control (containing wildtype humanized APP) are the first commercially available APP KI mice within the United States. While APPSAA mice have been shown to develop progressive Aβ pathology and neuroinflammation, the age at which behavioral and cognitive impairments begin to develop has yet to be described. Therefore, we performed an in-depth longitudinal study over 16 months, assessing cognition in these two strains, as well as assessments of motor function. While no cognitive deficits are observed in either genotype throughout the first year of life, 16-month-old APPSAA, but not APPWT mice show initial signs of spatial memory decline. In addition, both genotypes display impaired motor function at the same age. Together, this data identifies a timeframe where behavioral deficits appear, providing an essential foundation for future studies using these model systems. |
| format | Article |
| id | doaj-art-c784812e974547c393102f8559ff40b1 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-c784812e974547c393102f8559ff40b12025-02-09T12:31:48ZengNature PortfolioScientific Reports2045-23222025-02-011511810.1038/s41598-025-89051-8Longitudinal characterization reveals behavioral impairments in aged APP knock in mouse modelsLisa Blackmer-Raynolds0Lyndsey D. Lipson1Isabel Fraccaroli2Ian N. Krout3Jianjun Chang4Timothy Robert Sampson5Department of Cell Biology, Emory University School of MedicineDepartment of Cell Biology, Emory University School of MedicineDepartment of Cell Biology, Emory University School of MedicineDepartment of Cell Biology, Emory University School of MedicineDepartment of Cell Biology, Emory University School of MedicineDepartment of Cell Biology, Emory University School of MedicineAbstract APP knock-in (KI) mice serve as an exciting new model system to understand amyloid beta (Aβ) pathology, overcoming many of the limitations of previous overexpression-based model systems. The APPSAA mouse model (containing the humanized APP with three familial Alzheimer’s disease mutations) and the APPWT control (containing wildtype humanized APP) are the first commercially available APP KI mice within the United States. While APPSAA mice have been shown to develop progressive Aβ pathology and neuroinflammation, the age at which behavioral and cognitive impairments begin to develop has yet to be described. Therefore, we performed an in-depth longitudinal study over 16 months, assessing cognition in these two strains, as well as assessments of motor function. While no cognitive deficits are observed in either genotype throughout the first year of life, 16-month-old APPSAA, but not APPWT mice show initial signs of spatial memory decline. In addition, both genotypes display impaired motor function at the same age. Together, this data identifies a timeframe where behavioral deficits appear, providing an essential foundation for future studies using these model systems.https://doi.org/10.1038/s41598-025-89051-8Alzheimer’s diseaseCognitive behaviorAmyloid precursor proteinAnimal models |
| spellingShingle | Lisa Blackmer-Raynolds Lyndsey D. Lipson Isabel Fraccaroli Ian N. Krout Jianjun Chang Timothy Robert Sampson Longitudinal characterization reveals behavioral impairments in aged APP knock in mouse models Scientific Reports Alzheimer’s disease Cognitive behavior Amyloid precursor protein Animal models |
| title | Longitudinal characterization reveals behavioral impairments in aged APP knock in mouse models |
| title_full | Longitudinal characterization reveals behavioral impairments in aged APP knock in mouse models |
| title_fullStr | Longitudinal characterization reveals behavioral impairments in aged APP knock in mouse models |
| title_full_unstemmed | Longitudinal characterization reveals behavioral impairments in aged APP knock in mouse models |
| title_short | Longitudinal characterization reveals behavioral impairments in aged APP knock in mouse models |
| title_sort | longitudinal characterization reveals behavioral impairments in aged app knock in mouse models |
| topic | Alzheimer’s disease Cognitive behavior Amyloid precursor protein Animal models |
| url | https://doi.org/10.1038/s41598-025-89051-8 |
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