Impact of Cerebral Amyloid Angiopathy in Two Transgenic Mouse Models of Cerebral β-Amyloidosis: A Neuropathological Study
The pathological accumulation of parenchymal and vascular amyloid-beta (Aβ) are the main hallmarks of Alzheimer’s disease (AD) and Cerebral Amyloid Angiopathy (CAA), respectively. Emerging evidence raises an important contribution of vascular dysfunction in AD pathology that could partially explain...
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MDPI AG
2022-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/9/4972 |
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| author | Paula Marazuela Berta Paez-Montserrat Anna Bonaterra-Pastra Montse Solé Mar Hernández-Guillamon |
| author_facet | Paula Marazuela Berta Paez-Montserrat Anna Bonaterra-Pastra Montse Solé Mar Hernández-Guillamon |
| author_sort | Paula Marazuela |
| collection | DOAJ |
| description | The pathological accumulation of parenchymal and vascular amyloid-beta (Aβ) are the main hallmarks of Alzheimer’s disease (AD) and Cerebral Amyloid Angiopathy (CAA), respectively. Emerging evidence raises an important contribution of vascular dysfunction in AD pathology that could partially explain the failure of anti-Aβ therapies in this field. Transgenic mice models of cerebral β-amyloidosis are essential to a better understanding of the mechanisms underlying amyloid accumulation in the cerebrovasculature and its interactions with neuritic plaque deposition. Here, our main objective was to evaluate the progression of both parenchymal and vascular deposition in APP23 and 5xFAD transgenic mice in relation to age and sex. We first showed a significant age-dependent accumulation of extracellular Aβ deposits in both transgenic models, with a greater increase in APP23 females. We confirmed that CAA pathology was more prominent in the APP23 mice, demonstrating a higher progression of Aβ-positive vessels with age, but not linked to sex, and detecting a pronounced burden of cerebral microbleeds (cMBs) by magnetic resonance imaging (MRI). In contrast, 5xFAD mice did not present CAA, as shown by the negligible Aβ presence in cerebral vessels and the occurrence of occasional cMBs comparable to WT mice. In conclusion, the APP23 mouse model is an interesting tool to study the overlap between vascular and parenchymal Aβ deposition and to evaluate future disease-modifying therapy before its translation to the clinic. |
| first_indexed | 2024-03-10T04:05:36Z |
| format | Article |
| id | doaj.art-a7257fcbf62841b4a32b49bac6ba169d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:05:36Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a7257fcbf62841b4a32b49bac6ba169d2023-11-23T08:25:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01239497210.3390/ijms23094972Impact of Cerebral Amyloid Angiopathy in Two Transgenic Mouse Models of Cerebral β-Amyloidosis: A Neuropathological StudyPaula Marazuela0Berta Paez-Montserrat1Anna Bonaterra-Pastra2Montse Solé3Mar Hernández-Guillamon4Neurovascular Research Laboratory, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, 08035 Barcelona, SpainNeurovascular Research Laboratory, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, 08035 Barcelona, SpainNeurovascular Research Laboratory, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, 08035 Barcelona, SpainNeurovascular Research Laboratory, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, 08035 Barcelona, SpainNeurovascular Research Laboratory, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, 08035 Barcelona, SpainThe pathological accumulation of parenchymal and vascular amyloid-beta (Aβ) are the main hallmarks of Alzheimer’s disease (AD) and Cerebral Amyloid Angiopathy (CAA), respectively. Emerging evidence raises an important contribution of vascular dysfunction in AD pathology that could partially explain the failure of anti-Aβ therapies in this field. Transgenic mice models of cerebral β-amyloidosis are essential to a better understanding of the mechanisms underlying amyloid accumulation in the cerebrovasculature and its interactions with neuritic plaque deposition. Here, our main objective was to evaluate the progression of both parenchymal and vascular deposition in APP23 and 5xFAD transgenic mice in relation to age and sex. We first showed a significant age-dependent accumulation of extracellular Aβ deposits in both transgenic models, with a greater increase in APP23 females. We confirmed that CAA pathology was more prominent in the APP23 mice, demonstrating a higher progression of Aβ-positive vessels with age, but not linked to sex, and detecting a pronounced burden of cerebral microbleeds (cMBs) by magnetic resonance imaging (MRI). In contrast, 5xFAD mice did not present CAA, as shown by the negligible Aβ presence in cerebral vessels and the occurrence of occasional cMBs comparable to WT mice. In conclusion, the APP23 mouse model is an interesting tool to study the overlap between vascular and parenchymal Aβ deposition and to evaluate future disease-modifying therapy before its translation to the clinic.https://www.mdpi.com/1422-0067/23/9/4972APP235xFADcerebral β-amyloidosispreclinical MRIcerebral microbleeds |
| spellingShingle | Paula Marazuela Berta Paez-Montserrat Anna Bonaterra-Pastra Montse Solé Mar Hernández-Guillamon Impact of Cerebral Amyloid Angiopathy in Two Transgenic Mouse Models of Cerebral β-Amyloidosis: A Neuropathological Study International Journal of Molecular Sciences APP23 5xFAD cerebral β-amyloidosis preclinical MRI cerebral microbleeds |
| title | Impact of Cerebral Amyloid Angiopathy in Two Transgenic Mouse Models of Cerebral β-Amyloidosis: A Neuropathological Study |
| title_full | Impact of Cerebral Amyloid Angiopathy in Two Transgenic Mouse Models of Cerebral β-Amyloidosis: A Neuropathological Study |
| title_fullStr | Impact of Cerebral Amyloid Angiopathy in Two Transgenic Mouse Models of Cerebral β-Amyloidosis: A Neuropathological Study |
| title_full_unstemmed | Impact of Cerebral Amyloid Angiopathy in Two Transgenic Mouse Models of Cerebral β-Amyloidosis: A Neuropathological Study |
| title_short | Impact of Cerebral Amyloid Angiopathy in Two Transgenic Mouse Models of Cerebral β-Amyloidosis: A Neuropathological Study |
| title_sort | impact of cerebral amyloid angiopathy in two transgenic mouse models of cerebral β amyloidosis a neuropathological study |
| topic | APP23 5xFAD cerebral β-amyloidosis preclinical MRI cerebral microbleeds |
| url | https://www.mdpi.com/1422-0067/23/9/4972 |
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