The effect of Abi3 locus deletion on the progression of Alzheimer’s disease-related pathologies
Human genetics studies of Alzheimer’s disease (AD) have identified the ABI3 gene as a candidate risk gene for AD. Because ABI3 is highly expressed in microglia, the brain’s immune cells, it was suggested that ABI3 might impact AD pathogenesis by regulating the immune response. Recent studies suggest...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1102530/full |
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| author | Hande Karahan Hande Karahan Daniel C. Smith Daniel C. Smith Byungwook Kim Byungwook Kim Brianne McCord Brianne McCord Jordan Mantor Jordan Mantor Sutha K. John Sutha K. John Md Mamun Al-Amin Md Mamun Al-Amin Luke C. Dabin Luke C. Dabin Jungsu Kim Jungsu Kim Jungsu Kim |
| author_facet | Hande Karahan Hande Karahan Daniel C. Smith Daniel C. Smith Byungwook Kim Byungwook Kim Brianne McCord Brianne McCord Jordan Mantor Jordan Mantor Sutha K. John Sutha K. John Md Mamun Al-Amin Md Mamun Al-Amin Luke C. Dabin Luke C. Dabin Jungsu Kim Jungsu Kim Jungsu Kim |
| author_sort | Hande Karahan |
| collection | DOAJ |
| description | Human genetics studies of Alzheimer’s disease (AD) have identified the ABI3 gene as a candidate risk gene for AD. Because ABI3 is highly expressed in microglia, the brain’s immune cells, it was suggested that ABI3 might impact AD pathogenesis by regulating the immune response. Recent studies suggest that microglia have multifaceted roles in AD. Their immune response and phagocytosis functions can have beneficial effects in the early stages of AD by clearing up amyloid-beta (Aβ) plaques. However, they can be harmful at later stages due to their continuous inflammatory response. Therefore, it is important to understand the role of genes in microglia functions and their impact on AD pathologies along the progression of the disease. To determine the role of ABI3 at the early stage of amyloid pathology, we crossed Abi3 knock-out mice with the 5XFAD Aβ-amyloidosis mouse model and aged them until 4.5-month-old. Here, we demonstrate that deletion of the Abi3 locus increased Aβ plaque deposition, while there was no significant change in microgliosis and astrogliosis. Transcriptomic analysis indicates alterations in the expression of immune genes, such as Tyrobp, Fcer1g, and C1qa. In addition to the transcriptomic changes, we found elevated cytokine protein levels in Abi3 knock-out mouse brains, strengthening the role of ABI3 in neuroinflammation. These findings suggest that loss of ABI3 function may exacerbate AD progression by increasing Aβ accumulation and inflammation starting from earlier stages of the pathology. |
| first_indexed | 2024-04-10T09:12:09Z |
| format | Article |
| id | doaj.art-6efcf4a66fa64855ad808fa16b336f87 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T09:12:09Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-6efcf4a66fa64855ad808fa16b336f872023-02-21T04:44:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-02-011410.3389/fimmu.2023.11025301102530The effect of Abi3 locus deletion on the progression of Alzheimer’s disease-related pathologiesHande Karahan0Hande Karahan1Daniel C. Smith2Daniel C. Smith3Byungwook Kim4Byungwook Kim5Brianne McCord6Brianne McCord7Jordan Mantor8Jordan Mantor9Sutha K. John10Sutha K. John11Md Mamun Al-Amin12Md Mamun Al-Amin13Luke C. Dabin14Luke C. Dabin15Jungsu Kim16Jungsu Kim17Jungsu Kim18Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United StatesStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, United StatesMedical Neuroscience Graduate Program, Indiana University School of Medicine, Indianapolis, IN, United StatesStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United StatesStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United StatesStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United StatesStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United StatesStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United StatesStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United StatesStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United StatesMedical Neuroscience Graduate Program, Indiana University School of Medicine, Indianapolis, IN, United StatesHuman genetics studies of Alzheimer’s disease (AD) have identified the ABI3 gene as a candidate risk gene for AD. Because ABI3 is highly expressed in microglia, the brain’s immune cells, it was suggested that ABI3 might impact AD pathogenesis by regulating the immune response. Recent studies suggest that microglia have multifaceted roles in AD. Their immune response and phagocytosis functions can have beneficial effects in the early stages of AD by clearing up amyloid-beta (Aβ) plaques. However, they can be harmful at later stages due to their continuous inflammatory response. Therefore, it is important to understand the role of genes in microglia functions and their impact on AD pathologies along the progression of the disease. To determine the role of ABI3 at the early stage of amyloid pathology, we crossed Abi3 knock-out mice with the 5XFAD Aβ-amyloidosis mouse model and aged them until 4.5-month-old. Here, we demonstrate that deletion of the Abi3 locus increased Aβ plaque deposition, while there was no significant change in microgliosis and astrogliosis. Transcriptomic analysis indicates alterations in the expression of immune genes, such as Tyrobp, Fcer1g, and C1qa. In addition to the transcriptomic changes, we found elevated cytokine protein levels in Abi3 knock-out mouse brains, strengthening the role of ABI3 in neuroinflammation. These findings suggest that loss of ABI3 function may exacerbate AD progression by increasing Aβ accumulation and inflammation starting from earlier stages of the pathology.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1102530/fullABI3Alzheimer’s diseasemicrogliainflammation5xFAD |
| spellingShingle | Hande Karahan Hande Karahan Daniel C. Smith Daniel C. Smith Byungwook Kim Byungwook Kim Brianne McCord Brianne McCord Jordan Mantor Jordan Mantor Sutha K. John Sutha K. John Md Mamun Al-Amin Md Mamun Al-Amin Luke C. Dabin Luke C. Dabin Jungsu Kim Jungsu Kim Jungsu Kim The effect of Abi3 locus deletion on the progression of Alzheimer’s disease-related pathologies Frontiers in Immunology ABI3 Alzheimer’s disease microglia inflammation 5xFAD |
| title | The effect of Abi3 locus deletion on the progression of Alzheimer’s disease-related pathologies |
| title_full | The effect of Abi3 locus deletion on the progression of Alzheimer’s disease-related pathologies |
| title_fullStr | The effect of Abi3 locus deletion on the progression of Alzheimer’s disease-related pathologies |
| title_full_unstemmed | The effect of Abi3 locus deletion on the progression of Alzheimer’s disease-related pathologies |
| title_short | The effect of Abi3 locus deletion on the progression of Alzheimer’s disease-related pathologies |
| title_sort | effect of abi3 locus deletion on the progression of alzheimer s disease related pathologies |
| topic | ABI3 Alzheimer’s disease microglia inflammation 5xFAD |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1102530/full |
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