Deletion of Murine APP Aggravates Tau and Amyloid Pathologies in the 5xFADXTg30 Alzheimer’s Disease Model
Alzheimer’s disease is characterized by two key neuropathological lesions: amyloid plaques composed of amyloid β and neurofibrillary tangles formed by hyperphosphorylated tau. Amyloid β is produced through successive cleavages of amyloid precursor protein (APP) via the amyloidogenic pathway. While i...
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2025-01-01
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| author | Kunie Ando Andreea-Claudia Kosa Yasmina Mehadji Hinde Lasri Lidia Lopez-Gutierrez Carolina Quintanilla-Sánchez Emmanuel Aydin Emilie Doeraene Alain Wathelet-Depauw Siranjeevi Nagaraj Jean-Pierre Brion Karelle Leroy |
| author_facet | Kunie Ando Andreea-Claudia Kosa Yasmina Mehadji Hinde Lasri Lidia Lopez-Gutierrez Carolina Quintanilla-Sánchez Emmanuel Aydin Emilie Doeraene Alain Wathelet-Depauw Siranjeevi Nagaraj Jean-Pierre Brion Karelle Leroy |
| author_sort | Kunie Ando |
| collection | DOAJ |
| description | Alzheimer’s disease is characterized by two key neuropathological lesions: amyloid plaques composed of amyloid β and neurofibrillary tangles formed by hyperphosphorylated tau. Amyloid β is produced through successive cleavages of amyloid precursor protein (APP) via the amyloidogenic pathway. While increasing evidence suggests that APP plays critical roles in neuronal function and that its proteolytic derivative, sAPPα, has neurotrophic effects, the impact of APP deletion on both amyloid and tau pathologies remains poorly understood. Here, we introduce a novel transgenic mouse model, 5xFAD×Tg30XAPP-/-, in which murine APP is deleted in the presence of both amyloid and tau pathologies. Using this innovative model, we demonstrate for the first time that deletion of APP exacerbates tau aggregation, amyloid deposition, and gliosis compared to control 5xFAD×Tg30 mice. This study provides the first in vivo evidence that APP deletion has profound and detrimental effects on both amyloid and tau pathologies in a transgenic model of Alzheimer’s disease, highlighting the previously unappreciated role of APP in the regulation of these neurodegenerative processes. |
| format | Article |
| id | doaj-art-3ecf18be900a478e8040f5ca453783d9 |
| institution | DOAJ |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-3ecf18be900a478e8040f5ca453783d92025-08-20T02:44:36ZengMDPI AGBiomolecules2218-273X2025-01-0115215910.3390/biom15020159Deletion of Murine APP Aggravates Tau and Amyloid Pathologies in the 5xFADXTg30 Alzheimer’s Disease ModelKunie Ando0Andreea-Claudia Kosa1Yasmina Mehadji2Hinde Lasri3Lidia Lopez-Gutierrez4Carolina Quintanilla-Sánchez5Emmanuel Aydin6Emilie Doeraene7Alain Wathelet-Depauw8Siranjeevi Nagaraj9Jean-Pierre Brion10Karelle Leroy11Alzheimer and Other Tauopathies Research Group, ULB Neuroscience Institute (UNI), ULB Center for Diabetes Research (UCDR), Faculty of Medicine, Université Libre de Bruxelles, 808 Route de Lennik, Bldg GE, 1070 Brussels, BelgiumAlzheimer and Other Tauopathies Research Group, ULB Neuroscience Institute (UNI), ULB Center for Diabetes Research (UCDR), Faculty of Medicine, Université Libre de Bruxelles, 808 Route de Lennik, Bldg GE, 1070 Brussels, BelgiumAlzheimer and Other Tauopathies Research Group, ULB Neuroscience Institute (UNI), ULB Center for Diabetes Research (UCDR), Faculty of Medicine, Université Libre de Bruxelles, 808 Route de Lennik, Bldg GE, 1070 Brussels, BelgiumAlzheimer and Other Tauopathies Research Group, ULB Neuroscience Institute (UNI), ULB Center for Diabetes Research (UCDR), Faculty of Medicine, Université Libre de Bruxelles, 808 Route de Lennik, Bldg GE, 1070 Brussels, BelgiumAlzheimer and Other Tauopathies Research Group, ULB Neuroscience Institute (UNI), ULB Center for Diabetes Research (UCDR), Faculty of Medicine, Université Libre de Bruxelles, 808 Route de Lennik, Bldg GE, 1070 Brussels, BelgiumAlzheimer and Other Tauopathies Research Group, ULB Neuroscience Institute (UNI), ULB Center for Diabetes Research (UCDR), Faculty of Medicine, Université Libre de Bruxelles, 808 Route de Lennik, Bldg GE, 1070 Brussels, BelgiumAlzheimer and Other Tauopathies Research Group, ULB Neuroscience Institute (UNI), ULB Center for Diabetes Research (UCDR), Faculty of Medicine, Université Libre de Bruxelles, 808 Route de Lennik, Bldg GE, 1070 Brussels, BelgiumAlzheimer and Other Tauopathies Research Group, ULB Neuroscience Institute (UNI), ULB Center for Diabetes Research (UCDR), Faculty of Medicine, Université Libre de Bruxelles, 808 Route de Lennik, Bldg GE, 1070 Brussels, BelgiumAlzheimer and Other Tauopathies Research Group, ULB Neuroscience Institute (UNI), ULB Center for Diabetes Research (UCDR), Faculty of Medicine, Université Libre de Bruxelles, 808 Route de Lennik, Bldg GE, 1070 Brussels, BelgiumAlzheimer and Other Tauopathies Research Group, ULB Neuroscience Institute (UNI), ULB Center for Diabetes Research (UCDR), Faculty of Medicine, Université Libre de Bruxelles, 808 Route de Lennik, Bldg GE, 1070 Brussels, BelgiumAlzheimer and Other Tauopathies Research Group, ULB Neuroscience Institute (UNI), ULB Center for Diabetes Research (UCDR), Faculty of Medicine, Université Libre de Bruxelles, 808 Route de Lennik, Bldg GE, 1070 Brussels, BelgiumAlzheimer and Other Tauopathies Research Group, ULB Neuroscience Institute (UNI), ULB Center for Diabetes Research (UCDR), Faculty of Medicine, Université Libre de Bruxelles, 808 Route de Lennik, Bldg GE, 1070 Brussels, BelgiumAlzheimer’s disease is characterized by two key neuropathological lesions: amyloid plaques composed of amyloid β and neurofibrillary tangles formed by hyperphosphorylated tau. Amyloid β is produced through successive cleavages of amyloid precursor protein (APP) via the amyloidogenic pathway. While increasing evidence suggests that APP plays critical roles in neuronal function and that its proteolytic derivative, sAPPα, has neurotrophic effects, the impact of APP deletion on both amyloid and tau pathologies remains poorly understood. Here, we introduce a novel transgenic mouse model, 5xFAD×Tg30XAPP-/-, in which murine APP is deleted in the presence of both amyloid and tau pathologies. Using this innovative model, we demonstrate for the first time that deletion of APP exacerbates tau aggregation, amyloid deposition, and gliosis compared to control 5xFAD×Tg30 mice. This study provides the first in vivo evidence that APP deletion has profound and detrimental effects on both amyloid and tau pathologies in a transgenic model of Alzheimer’s disease, highlighting the previously unappreciated role of APP in the regulation of these neurodegenerative processes.https://www.mdpi.com/2218-273X/15/2/159Alzheimer’s diseaseamyloid precursor proteinamyloid βpTaugliosis |
| spellingShingle | Kunie Ando Andreea-Claudia Kosa Yasmina Mehadji Hinde Lasri Lidia Lopez-Gutierrez Carolina Quintanilla-Sánchez Emmanuel Aydin Emilie Doeraene Alain Wathelet-Depauw Siranjeevi Nagaraj Jean-Pierre Brion Karelle Leroy Deletion of Murine APP Aggravates Tau and Amyloid Pathologies in the 5xFADXTg30 Alzheimer’s Disease Model Biomolecules Alzheimer’s disease amyloid precursor protein amyloid β pTau gliosis |
| title | Deletion of Murine APP Aggravates Tau and Amyloid Pathologies in the 5xFADXTg30 Alzheimer’s Disease Model |
| title_full | Deletion of Murine APP Aggravates Tau and Amyloid Pathologies in the 5xFADXTg30 Alzheimer’s Disease Model |
| title_fullStr | Deletion of Murine APP Aggravates Tau and Amyloid Pathologies in the 5xFADXTg30 Alzheimer’s Disease Model |
| title_full_unstemmed | Deletion of Murine APP Aggravates Tau and Amyloid Pathologies in the 5xFADXTg30 Alzheimer’s Disease Model |
| title_short | Deletion of Murine APP Aggravates Tau and Amyloid Pathologies in the 5xFADXTg30 Alzheimer’s Disease Model |
| title_sort | deletion of murine app aggravates tau and amyloid pathologies in the 5xfadxtg30 alzheimer s disease model |
| topic | Alzheimer’s disease amyloid precursor protein amyloid β pTau gliosis |
| url | https://www.mdpi.com/2218-273X/15/2/159 |
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