Exploiting microglial and peripheral immune cell crosstalk to treat Alzheimer’s disease
Abstract Neuroinflammation is considered one of the cardinal features of Alzheimer’s disease (AD). Neuritic plaques composed of amyloid β and neurofibrillary tangle-laden neurons are surrounded by reactive astrocytes and microglia. Exposure of microglia, the resident myeloid cell of the CNS, to amyl...
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| Format: | Article |
| Language: | English |
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BMC
2019-04-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-019-1453-0 |
| _version_ | 1819108551746912256 |
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| author | Dawling A. Dionisio-Santos John A. Olschowka M. Kerry O’Banion |
| author_facet | Dawling A. Dionisio-Santos John A. Olschowka M. Kerry O’Banion |
| author_sort | Dawling A. Dionisio-Santos |
| collection | DOAJ |
| description | Abstract Neuroinflammation is considered one of the cardinal features of Alzheimer’s disease (AD). Neuritic plaques composed of amyloid β and neurofibrillary tangle-laden neurons are surrounded by reactive astrocytes and microglia. Exposure of microglia, the resident myeloid cell of the CNS, to amyloid β causes these cells to acquire an inflammatory phenotype. While these reactive microglia are important to contain and phagocytose amyloid plaques, their activated phenotype impacts CNS homeostasis. In rodent models, increased neuroinflammation promoted by overexpression of proinflammatory cytokines can cause an increase in hyperphosphorylated tau and a decrease in hippocampal function. The peripheral immune system can also play a detrimental or beneficial role in CNS inflammation. Systemic inflammation can increase the risk of developing AD dementia, and chemokines released directly by microglia or indirectly by endothelial cells can attract monocytes and T lymphocytes to the CNS. These peripheral immune cells can aid in amyloid β clearance or modulate microglia responses, depending on the cell type. As such, several groups have targeted the peripheral immune system to modulate chronic neuroinflammation. In this review, we focus on the interplay of immunomodulating factors and cell types that are being investigated as possible therapeutic targets for the treatment or prevention of AD. |
| first_indexed | 2024-12-22T03:11:44Z |
| format | Article |
| id | doaj.art-df43ab8fa06d4c18897474e58f70aada |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-22T03:11:44Z |
| publishDate | 2019-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-df43ab8fa06d4c18897474e58f70aada2022-12-21T18:40:55ZengBMCJournal of Neuroinflammation1742-20942019-04-0116111310.1186/s12974-019-1453-0Exploiting microglial and peripheral immune cell crosstalk to treat Alzheimer’s diseaseDawling A. Dionisio-Santos0John A. Olschowka1M. Kerry O’Banion2Department of Neuroscience, Del Monte Institute for Neuroscience, University of Rochester School of Medicine and DentistryDepartment of Neuroscience, Del Monte Institute for Neuroscience, University of Rochester School of Medicine and DentistryDepartment of Neuroscience, Del Monte Institute for Neuroscience, University of Rochester School of Medicine and DentistryAbstract Neuroinflammation is considered one of the cardinal features of Alzheimer’s disease (AD). Neuritic plaques composed of amyloid β and neurofibrillary tangle-laden neurons are surrounded by reactive astrocytes and microglia. Exposure of microglia, the resident myeloid cell of the CNS, to amyloid β causes these cells to acquire an inflammatory phenotype. While these reactive microglia are important to contain and phagocytose amyloid plaques, their activated phenotype impacts CNS homeostasis. In rodent models, increased neuroinflammation promoted by overexpression of proinflammatory cytokines can cause an increase in hyperphosphorylated tau and a decrease in hippocampal function. The peripheral immune system can also play a detrimental or beneficial role in CNS inflammation. Systemic inflammation can increase the risk of developing AD dementia, and chemokines released directly by microglia or indirectly by endothelial cells can attract monocytes and T lymphocytes to the CNS. These peripheral immune cells can aid in amyloid β clearance or modulate microglia responses, depending on the cell type. As such, several groups have targeted the peripheral immune system to modulate chronic neuroinflammation. In this review, we focus on the interplay of immunomodulating factors and cell types that are being investigated as possible therapeutic targets for the treatment or prevention of AD.http://link.springer.com/article/10.1186/s12974-019-1453-0Alzheimer’s diseaseMicrogliaCytokinesInnate immunityAdaptive immunityTherapeutics |
| spellingShingle | Dawling A. Dionisio-Santos John A. Olschowka M. Kerry O’Banion Exploiting microglial and peripheral immune cell crosstalk to treat Alzheimer’s disease Journal of Neuroinflammation Alzheimer’s disease Microglia Cytokines Innate immunity Adaptive immunity Therapeutics |
| title | Exploiting microglial and peripheral immune cell crosstalk to treat Alzheimer’s disease |
| title_full | Exploiting microglial and peripheral immune cell crosstalk to treat Alzheimer’s disease |
| title_fullStr | Exploiting microglial and peripheral immune cell crosstalk to treat Alzheimer’s disease |
| title_full_unstemmed | Exploiting microglial and peripheral immune cell crosstalk to treat Alzheimer’s disease |
| title_short | Exploiting microglial and peripheral immune cell crosstalk to treat Alzheimer’s disease |
| title_sort | exploiting microglial and peripheral immune cell crosstalk to treat alzheimer s disease |
| topic | Alzheimer’s disease Microglia Cytokines Innate immunity Adaptive immunity Therapeutics |
| url | http://link.springer.com/article/10.1186/s12974-019-1453-0 |
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