The role of immunity and neuroinflammation in genetic predisposition and pathogenesis of Alzheimer's disease
Alzheimer's disease is an important public concern with rising prevalence across the globe. While many therapeutic approaches for Alzheimer's disease have been developed, there are currently no validated disease-modifying treatments. Thus, in order to develop novel treatment strategies, th...
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| Format: | Article |
| Language: | English |
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AIMS Press
2015-09-01
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| Series: | AIMS Genetics |
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| Online Access: | http://www.aimspress.com/Genetics/article/449/fulltext.html |
| _version_ | 1830188120258117632 |
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| author | Seoyoung Yoon Yong-Ku Kim |
| author_facet | Seoyoung Yoon Yong-Ku Kim |
| author_sort | Seoyoung Yoon |
| collection | DOAJ |
| description | Alzheimer's disease is an important public concern with rising prevalence across the globe. While many therapeutic approaches for Alzheimer's disease have been developed, there are currently no validated disease-modifying treatments. Thus, in order to develop novel treatment strategies, there is a significant need to progress our understanding of the pathogenesis of Alzheimer's disease. Several large genome-wide association studies and whole genome and exome sequencing studies have identified novel genes associated with late-onset Alzheimer's disease. Interestingly, many of the genes are associated with inflammation and the immune system, including complement receptor 1, clusterin, CD33, EPH receptor A1, membrane-spanning 4-domains subfamily A, ATP-binding cassette sub-family A member 7, major histocompatibility complex class II, inositol polyphosphate-5-phosphatase, myocyte enhancer factor 2C, and triggering receptor expressed on myeloid cells 2. The pathogenetic contributions of immune reaction and neuroinflammation in Alzheimer's disease have been regarded largely as part of amyloid cascade hypothesis. The neurotoxic amyloid-β (Aβ) induces activation of immune cells, such as microglia, astrocytes, perivascular macrophages and lymphocytes and decreased capability of clearing Aβ by immune system and chronic inflammation caused by activated immune cells aggravate neuronal damage and eventually Alzheimer's disease. But the precise mechanism and hereditary impact on such process is largely unknown. The current findings in genetic studies suggest that the immunological mechanisms of Alzheimer's disease may extend beyond passive reaction of Aβ, including the development of Alzheimer's disease such as time of onset and rate of progression. In this article, we aimed to review the mechanisms of immune reaction and neuroinflammation in Alzheimer's disease, with an emphasis on the function of genes known to be associated with a risk of Alzheimer's disease in terms of neuroinflammation and immune function. |
| first_indexed | 2024-12-17T22:40:33Z |
| format | Article |
| id | doaj.art-52e2f8dc44e14273b1173508cd6965ab |
| institution | Directory Open Access Journal |
| issn | 2377-1143 |
| language | English |
| last_indexed | 2024-12-17T22:40:33Z |
| publishDate | 2015-09-01 |
| publisher | AIMS Press |
| record_format | Article |
| series | AIMS Genetics |
| spelling | doaj.art-52e2f8dc44e14273b1173508cd6965ab2022-12-21T21:29:58ZengAIMS PressAIMS Genetics2377-11432015-09-012323024910.3934/genet.2015.3.230201503230The role of immunity and neuroinflammation in genetic predisposition and pathogenesis of Alzheimer's diseaseSeoyoung Yoon0Yong-Ku Kim1Department of Psychiatry, Korea University Ansan Hospital, Ansan, Republic of KoreaDepartment of Psychiatry, Korea University Ansan Hospital, Ansan, Republic of KoreaAlzheimer's disease is an important public concern with rising prevalence across the globe. While many therapeutic approaches for Alzheimer's disease have been developed, there are currently no validated disease-modifying treatments. Thus, in order to develop novel treatment strategies, there is a significant need to progress our understanding of the pathogenesis of Alzheimer's disease. Several large genome-wide association studies and whole genome and exome sequencing studies have identified novel genes associated with late-onset Alzheimer's disease. Interestingly, many of the genes are associated with inflammation and the immune system, including complement receptor 1, clusterin, CD33, EPH receptor A1, membrane-spanning 4-domains subfamily A, ATP-binding cassette sub-family A member 7, major histocompatibility complex class II, inositol polyphosphate-5-phosphatase, myocyte enhancer factor 2C, and triggering receptor expressed on myeloid cells 2. The pathogenetic contributions of immune reaction and neuroinflammation in Alzheimer's disease have been regarded largely as part of amyloid cascade hypothesis. The neurotoxic amyloid-β (Aβ) induces activation of immune cells, such as microglia, astrocytes, perivascular macrophages and lymphocytes and decreased capability of clearing Aβ by immune system and chronic inflammation caused by activated immune cells aggravate neuronal damage and eventually Alzheimer's disease. But the precise mechanism and hereditary impact on such process is largely unknown. The current findings in genetic studies suggest that the immunological mechanisms of Alzheimer's disease may extend beyond passive reaction of Aβ, including the development of Alzheimer's disease such as time of onset and rate of progression. In this article, we aimed to review the mechanisms of immune reaction and neuroinflammation in Alzheimer's disease, with an emphasis on the function of genes known to be associated with a risk of Alzheimer's disease in terms of neuroinflammation and immune function.http://www.aimspress.com/Genetics/article/449/fulltext.htmlAlzheimer's diseaseneuroinflammationimmunemicrogliagenetics |
| spellingShingle | Seoyoung Yoon Yong-Ku Kim The role of immunity and neuroinflammation in genetic predisposition and pathogenesis of Alzheimer's disease AIMS Genetics Alzheimer's disease neuroinflammation immune microglia genetics |
| title | The role of immunity and neuroinflammation in genetic predisposition and pathogenesis of Alzheimer's disease |
| title_full | The role of immunity and neuroinflammation in genetic predisposition and pathogenesis of Alzheimer's disease |
| title_fullStr | The role of immunity and neuroinflammation in genetic predisposition and pathogenesis of Alzheimer's disease |
| title_full_unstemmed | The role of immunity and neuroinflammation in genetic predisposition and pathogenesis of Alzheimer's disease |
| title_short | The role of immunity and neuroinflammation in genetic predisposition and pathogenesis of Alzheimer's disease |
| title_sort | role of immunity and neuroinflammation in genetic predisposition and pathogenesis of alzheimer s disease |
| topic | Alzheimer's disease neuroinflammation immune microglia genetics |
| url | http://www.aimspress.com/Genetics/article/449/fulltext.html |
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