Multi-functional role of apolipoprotein E in neurodegenerative diseases
Genetic diversity in the apolipoprotein E (ApoE) gene has been identified as the major susceptibility genetic risk factor for sporadic Alzheimer’s disease (SAD). Specifically, the ApoEε4 allele is a significant risk factor for SAD, while ApoEε2 allele provides protection compared to the more common...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2025.1535280/full |
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| author | Sadequl Islam Arshad Noorani Yang Sun Makoto Michikawa Kun Zou |
| author_facet | Sadequl Islam Arshad Noorani Yang Sun Makoto Michikawa Kun Zou |
| author_sort | Sadequl Islam |
| collection | DOAJ |
| description | Genetic diversity in the apolipoprotein E (ApoE) gene has been identified as the major susceptibility genetic risk factor for sporadic Alzheimer’s disease (SAD). Specifically, the ApoEε4 allele is a significant risk factor for SAD, while ApoEε2 allele provides protection compared to the more common ApoEε3 allele. This review discusses the role of the ApoE in AD and other neurodegenerative disorders. ApoE, a cholesterol transport protein, influences several pathways involved in neurodegeneration, particularly in AD. Beyond its established role in amyloid β-protein (Aβ) metabolism and deposition, ApoE also impacts tau pathology, neurodegeneration, and the microglial response to AD. The review aims to provide an updated overview of ApoE’s diverse roles, emphasizing its involvement in Aβ clearance through ApoE receptors. It also covers ApoE’s influence in other neurodegenerative diseases like Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Huntington’s disease (HD), vascular dementia (VD), and multiple sclerosis (MS). New research highlights the interaction between ApoE and presenilin (PS), suggesting connections between familial AD (FAD) and SAD. The review also explores protective effects of ApoE mutations against AD and ApoE4-induced tauopathy, neurodegeneration, and neuroinflammation. The insights from this comprehensive update could indeed lead to new therapeutic strategies for neurodegenerative diseases. |
| format | Article |
| id | doaj-art-fc478603f5994e15a0678b591c15c058 |
| institution | Kabale University |
| issn | 1663-4365 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Aging Neuroscience |
| spelling | doaj-art-fc478603f5994e15a0678b591c15c0582025-01-29T06:45:36ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652025-01-011710.3389/fnagi.2025.15352801535280Multi-functional role of apolipoprotein E in neurodegenerative diseasesSadequl Islam0Arshad Noorani1Yang Sun2Makoto Michikawa3Kun Zou4Department of Neuro-Oncology, Graduate School of Medical Sciences, Institute of Brain Science, Nagoya City University, Nagoya, JapanDepartment of Medicinal Chemistry, University of Kansas, Lawrence, KS, United StatesDepartment of Neuro-Oncology, Graduate School of Medical Sciences, Institute of Brain Science, Nagoya City University, Nagoya, JapanDepartment of Geriatric Medicine, School of Life Dentistry at Niigata, The Nippon Dental University, Niigata, JapanDepartment of Neuro-Oncology, Graduate School of Medical Sciences, Institute of Brain Science, Nagoya City University, Nagoya, JapanGenetic diversity in the apolipoprotein E (ApoE) gene has been identified as the major susceptibility genetic risk factor for sporadic Alzheimer’s disease (SAD). Specifically, the ApoEε4 allele is a significant risk factor for SAD, while ApoEε2 allele provides protection compared to the more common ApoEε3 allele. This review discusses the role of the ApoE in AD and other neurodegenerative disorders. ApoE, a cholesterol transport protein, influences several pathways involved in neurodegeneration, particularly in AD. Beyond its established role in amyloid β-protein (Aβ) metabolism and deposition, ApoE also impacts tau pathology, neurodegeneration, and the microglial response to AD. The review aims to provide an updated overview of ApoE’s diverse roles, emphasizing its involvement in Aβ clearance through ApoE receptors. It also covers ApoE’s influence in other neurodegenerative diseases like Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Huntington’s disease (HD), vascular dementia (VD), and multiple sclerosis (MS). New research highlights the interaction between ApoE and presenilin (PS), suggesting connections between familial AD (FAD) and SAD. The review also explores protective effects of ApoE mutations against AD and ApoE4-induced tauopathy, neurodegeneration, and neuroinflammation. The insights from this comprehensive update could indeed lead to new therapeutic strategies for neurodegenerative diseases.https://www.frontiersin.org/articles/10.3389/fnagi.2025.1535280/fullapolipoprotein EAlzheimer’s diseaseamyloid-β (Aβ)Parkinson’s diseaseamyotrophic lateral sclerosisneurodegenerative diseases |
| spellingShingle | Sadequl Islam Arshad Noorani Yang Sun Makoto Michikawa Kun Zou Multi-functional role of apolipoprotein E in neurodegenerative diseases Frontiers in Aging Neuroscience apolipoprotein E Alzheimer’s disease amyloid-β (Aβ) Parkinson’s disease amyotrophic lateral sclerosis neurodegenerative diseases |
| title | Multi-functional role of apolipoprotein E in neurodegenerative diseases |
| title_full | Multi-functional role of apolipoprotein E in neurodegenerative diseases |
| title_fullStr | Multi-functional role of apolipoprotein E in neurodegenerative diseases |
| title_full_unstemmed | Multi-functional role of apolipoprotein E in neurodegenerative diseases |
| title_short | Multi-functional role of apolipoprotein E in neurodegenerative diseases |
| title_sort | multi functional role of apolipoprotein e in neurodegenerative diseases |
| topic | apolipoprotein E Alzheimer’s disease amyloid-β (Aβ) Parkinson’s disease amyotrophic lateral sclerosis neurodegenerative diseases |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2025.1535280/full |
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