In‐Depth Cell‐Type‐Specific Proteome Landscape of the Brain from Human Amyloid‐β Overexpression Mouse Model
Abstract Amyloid‐β (Aβ) plays a crucial role in Alzheimer's disease pathogenesis. Understanding how Aβ overexpression alters the proteome of individual brain cell types is essential but challenging due to the nature of brain tissue, which contains intermingled various cell types. The current me...
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| Format: | Article |
| Language: | English |
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Wiley
2025-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202409318 |
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| author | Taekyung Ryu Seok‐Young Kim Thujitha Thuraisamy Jisu Shin Yura Jang Tae‐In Kam Chan Hyun Na |
| author_facet | Taekyung Ryu Seok‐Young Kim Thujitha Thuraisamy Jisu Shin Yura Jang Tae‐In Kam Chan Hyun Na |
| author_sort | Taekyung Ryu |
| collection | DOAJ |
| description | Abstract Amyloid‐β (Aβ) plays a crucial role in Alzheimer's disease pathogenesis. Understanding how Aβ overexpression alters the proteome of individual brain cell types is essential but challenging due to the nature of brain tissue, which contains intermingled various cell types. The current methods for cell‐type‐specific proteomics either require genetic modifications or complex cell isolation, limiting their use. This study introduces a novel method, in situ cell‐type‐specific proteome analysis using antibody‐mediated biotinylation (iCAB), which applies immunohistochemistry with biotin‐tyramide to target cell‐specific proteins directly in tissue. Applied to 5xFAD mice, iCAB enables us to identify ≈8000 cell‐type‐specific proteomes with significantly more differentially expressed proteins than traditional bulk proteome methods, pinpointing unique pathways such as mRNA processing, calcium regulation, and phagocytosis for neurons, astrocytes, and microglia, respectively. This study reports in‐depth the cell‐type‐specific brain proteome landscape of the human Aβ overexpression mouse model for the first time using an innovative tool that is powerful, straightforward, and applicable to both animal models and human tissues, without the need for prior genetic alterations. |
| format | Article |
| id | doaj-art-a99741c90e5b4c8fb94bbdaa041fef80 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-a99741c90e5b4c8fb94bbdaa041fef802025-08-20T02:02:16ZengWileyAdvanced Science2198-38442025-05-011220n/an/a10.1002/advs.202409318In‐Depth Cell‐Type‐Specific Proteome Landscape of the Brain from Human Amyloid‐β Overexpression Mouse ModelTaekyung Ryu0Seok‐Young Kim1Thujitha Thuraisamy2Jisu Shin3Yura Jang4Tae‐In Kam5Chan Hyun Na6Department of Neurology Johns Hopkins University School of Medicine Baltimore MD 21205 USADepartment of Neurology Johns Hopkins University School of Medicine Baltimore MD 21205 USADepartment of Neurology Johns Hopkins University School of Medicine Baltimore MD 21205 USADepartment of Neurology Johns Hopkins University School of Medicine Baltimore MD 21205 USADepartment of Neurology Johns Hopkins University School of Medicine Baltimore MD 21205 USADepartment of Neurology Johns Hopkins University School of Medicine Baltimore MD 21205 USADepartment of Neurology Johns Hopkins University School of Medicine Baltimore MD 21205 USAAbstract Amyloid‐β (Aβ) plays a crucial role in Alzheimer's disease pathogenesis. Understanding how Aβ overexpression alters the proteome of individual brain cell types is essential but challenging due to the nature of brain tissue, which contains intermingled various cell types. The current methods for cell‐type‐specific proteomics either require genetic modifications or complex cell isolation, limiting their use. This study introduces a novel method, in situ cell‐type‐specific proteome analysis using antibody‐mediated biotinylation (iCAB), which applies immunohistochemistry with biotin‐tyramide to target cell‐specific proteins directly in tissue. Applied to 5xFAD mice, iCAB enables us to identify ≈8000 cell‐type‐specific proteomes with significantly more differentially expressed proteins than traditional bulk proteome methods, pinpointing unique pathways such as mRNA processing, calcium regulation, and phagocytosis for neurons, astrocytes, and microglia, respectively. This study reports in‐depth the cell‐type‐specific brain proteome landscape of the human Aβ overexpression mouse model for the first time using an innovative tool that is powerful, straightforward, and applicable to both animal models and human tissues, without the need for prior genetic alterations.https://doi.org/10.1002/advs.202409318biotin‐tyramidesbrainscell‐type‐specific proteomesiCABbiotinylationimmunohistochemistry |
| spellingShingle | Taekyung Ryu Seok‐Young Kim Thujitha Thuraisamy Jisu Shin Yura Jang Tae‐In Kam Chan Hyun Na In‐Depth Cell‐Type‐Specific Proteome Landscape of the Brain from Human Amyloid‐β Overexpression Mouse Model Advanced Science biotin‐tyramides brains cell‐type‐specific proteomes iCAB biotinylation immunohistochemistry |
| title | In‐Depth Cell‐Type‐Specific Proteome Landscape of the Brain from Human Amyloid‐β Overexpression Mouse Model |
| title_full | In‐Depth Cell‐Type‐Specific Proteome Landscape of the Brain from Human Amyloid‐β Overexpression Mouse Model |
| title_fullStr | In‐Depth Cell‐Type‐Specific Proteome Landscape of the Brain from Human Amyloid‐β Overexpression Mouse Model |
| title_full_unstemmed | In‐Depth Cell‐Type‐Specific Proteome Landscape of the Brain from Human Amyloid‐β Overexpression Mouse Model |
| title_short | In‐Depth Cell‐Type‐Specific Proteome Landscape of the Brain from Human Amyloid‐β Overexpression Mouse Model |
| title_sort | in depth cell type specific proteome landscape of the brain from human amyloid β overexpression mouse model |
| topic | biotin‐tyramides brains cell‐type‐specific proteomes iCAB biotinylation immunohistochemistry |
| url | https://doi.org/10.1002/advs.202409318 |
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