APOE2: protective mechanism and therapeutic implications for Alzheimer’s disease
Abstract Investigations of apolipoprotein E (APOE) gene, the major genetic risk modifier for Alzheimer’s disease (AD), have yielded significant insights into the pathogenic mechanism. Among the three common coding variants, APOE*ε4 increases, whereas APOE*ε2 decreases the risk of late-onset AD compa...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-11-01
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| Series: | Molecular Neurodegeneration |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13024-020-00413-4 |
| _version_ | 1818269417062006784 |
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| author | Zonghua Li Francis Shue Na Zhao Mitsuru Shinohara Guojun Bu |
| author_facet | Zonghua Li Francis Shue Na Zhao Mitsuru Shinohara Guojun Bu |
| author_sort | Zonghua Li |
| collection | DOAJ |
| description | Abstract Investigations of apolipoprotein E (APOE) gene, the major genetic risk modifier for Alzheimer’s disease (AD), have yielded significant insights into the pathogenic mechanism. Among the three common coding variants, APOE*ε4 increases, whereas APOE*ε2 decreases the risk of late-onset AD compared with APOE*ε3. Despite increased understanding of the detrimental effect of APOE*ε4, it remains unclear how APOE*ε2 confers protection against AD. Accumulating evidence suggests that APOE*ε2 protects against AD through both amyloid-β (Aβ)-dependent and independent mechanisms. In addition, APOE*ε2 has been identified as a longevity gene, suggesting a systemic effect of APOE*ε2 on the aging process. However, APOE*ε2 is not entirely benign; APOE*ε2 carriers exhibit increased risk of certain cerebrovascular diseases and neurological disorders. Here, we review evidence from both human and animal studies demonstrating the protective effect of APOE*ε2 against AD and propose a working model depicting potential underlying mechanisms. Finally, we discuss potential therapeutic strategies designed to leverage the protective effect of APOE2 to treat AD. |
| first_indexed | 2024-12-12T20:54:03Z |
| format | Article |
| id | doaj.art-36de4881a3f6494a83af09590ed383ae |
| institution | Directory Open Access Journal |
| issn | 1750-1326 |
| language | English |
| last_indexed | 2024-12-12T20:54:03Z |
| publishDate | 2020-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Neurodegeneration |
| spelling | doaj.art-36de4881a3f6494a83af09590ed383ae2022-12-22T00:12:20ZengBMCMolecular Neurodegeneration1750-13262020-11-0115111910.1186/s13024-020-00413-4APOE2: protective mechanism and therapeutic implications for Alzheimer’s diseaseZonghua Li0Francis Shue1Na Zhao2Mitsuru Shinohara3Guojun Bu4Department of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Aging Neurobiology, National Center for Geriatrics and GerontologyDepartment of Neuroscience, Mayo ClinicAbstract Investigations of apolipoprotein E (APOE) gene, the major genetic risk modifier for Alzheimer’s disease (AD), have yielded significant insights into the pathogenic mechanism. Among the three common coding variants, APOE*ε4 increases, whereas APOE*ε2 decreases the risk of late-onset AD compared with APOE*ε3. Despite increased understanding of the detrimental effect of APOE*ε4, it remains unclear how APOE*ε2 confers protection against AD. Accumulating evidence suggests that APOE*ε2 protects against AD through both amyloid-β (Aβ)-dependent and independent mechanisms. In addition, APOE*ε2 has been identified as a longevity gene, suggesting a systemic effect of APOE*ε2 on the aging process. However, APOE*ε2 is not entirely benign; APOE*ε2 carriers exhibit increased risk of certain cerebrovascular diseases and neurological disorders. Here, we review evidence from both human and animal studies demonstrating the protective effect of APOE*ε2 against AD and propose a working model depicting potential underlying mechanisms. Finally, we discuss potential therapeutic strategies designed to leverage the protective effect of APOE2 to treat AD.http://link.springer.com/article/10.1186/s13024-020-00413-4Apolipoprotein E2Alzheimer’s diseaseAmyloid-βCerebrovascular diseaseLipid metabolismLongevity |
| spellingShingle | Zonghua Li Francis Shue Na Zhao Mitsuru Shinohara Guojun Bu APOE2: protective mechanism and therapeutic implications for Alzheimer’s disease Molecular Neurodegeneration Apolipoprotein E2 Alzheimer’s disease Amyloid-β Cerebrovascular disease Lipid metabolism Longevity |
| title | APOE2: protective mechanism and therapeutic implications for Alzheimer’s disease |
| title_full | APOE2: protective mechanism and therapeutic implications for Alzheimer’s disease |
| title_fullStr | APOE2: protective mechanism and therapeutic implications for Alzheimer’s disease |
| title_full_unstemmed | APOE2: protective mechanism and therapeutic implications for Alzheimer’s disease |
| title_short | APOE2: protective mechanism and therapeutic implications for Alzheimer’s disease |
| title_sort | apoe2 protective mechanism and therapeutic implications for alzheimer s disease |
| topic | Apolipoprotein E2 Alzheimer’s disease Amyloid-β Cerebrovascular disease Lipid metabolism Longevity |
| url | http://link.springer.com/article/10.1186/s13024-020-00413-4 |
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