Cargando…
The Major Risk Factors for Alzheimer’s Disease: Age, Sex, and Genes Modulate the Microglia Response to Aβ Plaques
Gene expression profiles of more than 10,000 individual microglial cells isolated from cortex and hippocampus of male and female App(NL-G-F) mice over time demonstrate that progressive amyloid-b accumulation accelerates two main activated microglia states that are also present during normal aging. A...
| Autores principales: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2019
|
| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340153/ https://www.ncbi.nlm.nih.gov/pubmed/31018141 http://dx.doi.org/10.1016/j.celrep.2019.03.099 |
| _version_ | 1783554997474033664 |
|---|---|
| author | Frigerio, Carlo Sala Wolfs, Leen Fattorelli, Nicola Thrupp, Nicola Voytyuk, Iryna Schmidt, Inga Mancuso, Renzo Chen, Wei-Ting Woodbury, Maya E. Srivastava, Gyan Möller, Thomas Hudry, Eloise Das, Sudeshna Saido, Takaomi Karran, Eric Hyman, Bradley Perry, V. Hugh Fiers, Mark De Strooper, Bart |
| author_facet | Frigerio, Carlo Sala Wolfs, Leen Fattorelli, Nicola Thrupp, Nicola Voytyuk, Iryna Schmidt, Inga Mancuso, Renzo Chen, Wei-Ting Woodbury, Maya E. Srivastava, Gyan Möller, Thomas Hudry, Eloise Das, Sudeshna Saido, Takaomi Karran, Eric Hyman, Bradley Perry, V. Hugh Fiers, Mark De Strooper, Bart |
| author_sort | Frigerio, Carlo Sala |
| collection | PubMed |
| description | Gene expression profiles of more than 10,000 individual microglial cells isolated from cortex and hippocampus of male and female App(NL-G-F) mice over time demonstrate that progressive amyloid-b accumulation accelerates two main activated microglia states that are also present during normal aging. Activated response microglia (ARMs) are composed of specialized subgroups overexpressing MHC type II and putative tissue repair genes (Dkk2, Gpnmb, and Spp1) and are strongly enriched with Alzheimer’s disease (AD) risk genes. Microglia from female mice progress faster in this activation trajectory. Similar activated states are also found in a second AD model and in human brain. Apoe, the major genetic risk factor for AD, regulates the ARMs but not the interferon response microglia (IRMs). Thus, the ARMs response is the converging point for aging, sex, and genetic AD risk factors. |
| format | Online Article Text |
| id | pubmed-7340153 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2019 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-73401532020-07-07 The Major Risk Factors for Alzheimer’s Disease: Age, Sex, and Genes Modulate the Microglia Response to Aβ Plaques Frigerio, Carlo Sala Wolfs, Leen Fattorelli, Nicola Thrupp, Nicola Voytyuk, Iryna Schmidt, Inga Mancuso, Renzo Chen, Wei-Ting Woodbury, Maya E. Srivastava, Gyan Möller, Thomas Hudry, Eloise Das, Sudeshna Saido, Takaomi Karran, Eric Hyman, Bradley Perry, V. Hugh Fiers, Mark De Strooper, Bart Cell Rep Article Gene expression profiles of more than 10,000 individual microglial cells isolated from cortex and hippocampus of male and female App(NL-G-F) mice over time demonstrate that progressive amyloid-b accumulation accelerates two main activated microglia states that are also present during normal aging. Activated response microglia (ARMs) are composed of specialized subgroups overexpressing MHC type II and putative tissue repair genes (Dkk2, Gpnmb, and Spp1) and are strongly enriched with Alzheimer’s disease (AD) risk genes. Microglia from female mice progress faster in this activation trajectory. Similar activated states are also found in a second AD model and in human brain. Apoe, the major genetic risk factor for AD, regulates the ARMs but not the interferon response microglia (IRMs). Thus, the ARMs response is the converging point for aging, sex, and genetic AD risk factors. 2019-04-23 /pmc/articles/PMC7340153/ /pubmed/31018141 http://dx.doi.org/10.1016/j.celrep.2019.03.099 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| spellingShingle | Article Frigerio, Carlo Sala Wolfs, Leen Fattorelli, Nicola Thrupp, Nicola Voytyuk, Iryna Schmidt, Inga Mancuso, Renzo Chen, Wei-Ting Woodbury, Maya E. Srivastava, Gyan Möller, Thomas Hudry, Eloise Das, Sudeshna Saido, Takaomi Karran, Eric Hyman, Bradley Perry, V. Hugh Fiers, Mark De Strooper, Bart The Major Risk Factors for Alzheimer’s Disease: Age, Sex, and Genes Modulate the Microglia Response to Aβ Plaques |
| title | The Major Risk Factors for Alzheimer’s Disease: Age, Sex, and Genes Modulate the Microglia Response to Aβ Plaques |
| title_full | The Major Risk Factors for Alzheimer’s Disease: Age, Sex, and Genes Modulate the Microglia Response to Aβ Plaques |
| title_fullStr | The Major Risk Factors for Alzheimer’s Disease: Age, Sex, and Genes Modulate the Microglia Response to Aβ Plaques |
| title_full_unstemmed | The Major Risk Factors for Alzheimer’s Disease: Age, Sex, and Genes Modulate the Microglia Response to Aβ Plaques |
| title_short | The Major Risk Factors for Alzheimer’s Disease: Age, Sex, and Genes Modulate the Microglia Response to Aβ Plaques |
| title_sort | major risk factors for alzheimer’s disease: age, sex, and genes modulate the microglia response to aβ plaques |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340153/ https://www.ncbi.nlm.nih.gov/pubmed/31018141 http://dx.doi.org/10.1016/j.celrep.2019.03.099 |
| work_keys_str_mv | AT frigeriocarlosala themajorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT wolfsleen themajorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT fattorellinicola themajorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT thruppnicola themajorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT voytyukiryna themajorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT schmidtinga themajorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT mancusorenzo themajorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT chenweiting themajorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT woodburymayae themajorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT srivastavagyan themajorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT mollerthomas themajorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT hudryeloise themajorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT dassudeshna themajorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT saidotakaomi themajorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT karraneric themajorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT hymanbradley themajorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT perryvhugh themajorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT fiersmark themajorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT destrooperbart themajorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT frigeriocarlosala majorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT wolfsleen majorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT fattorellinicola majorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT thruppnicola majorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT voytyukiryna majorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT schmidtinga majorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT mancusorenzo majorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT chenweiting majorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT woodburymayae majorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT srivastavagyan majorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT mollerthomas majorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT hudryeloise majorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT dassudeshna majorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT saidotakaomi majorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT karraneric majorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT hymanbradley majorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT perryvhugh majorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT fiersmark majorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques AT destrooperbart majorriskfactorsforalzheimersdiseaseagesexandgenesmodulatethemicrogliaresponsetoabplaques |