Mosi Li, Kris Holt, Katherine Ridley, Jing Qiu, Kirsty Haddow, Deepali Vasoya, Xin He, J. Tulloch, Declan King, David A. Hume, Clare Pridans, O. Dando, Tara L Spires-Jones, Giles E. Hardingham
{"title":"Microglia determine ß-amyloid plaque burden but are non-essential for downstream pathology","authors":"Mosi Li, Kris Holt, Katherine Ridley, Jing Qiu, Kirsty Haddow, Deepali Vasoya, Xin He, J. Tulloch, Declan King, David A. Hume, Clare Pridans, O. Dando, Tara L Spires-Jones, Giles E. Hardingham","doi":"10.1101/2024.08.06.606795","DOIUrl":null,"url":null,"abstract":"Evidence points to a role for microglia in Alzheimer’s disease (AD) risk, although their position in the pathological cascade is incompletely understood, prompting us to generate a model of ß-amyloidopathy lacking microglia. We find evidence that microglia promote plaque formation and creation of an Aß fibril-rich zone surrounding the plaque core. However, plaque-proximal reactive astrogliosis, synapse loss, and neurite dystrophy are still observed in the absence of microglia.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"bioRxiv","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2024.08.06.606795","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Evidence points to a role for microglia in Alzheimer’s disease (AD) risk, although their position in the pathological cascade is incompletely understood, prompting us to generate a model of ß-amyloidopathy lacking microglia. We find evidence that microglia promote plaque formation and creation of an Aß fibril-rich zone surrounding the plaque core. However, plaque-proximal reactive astrogliosis, synapse loss, and neurite dystrophy are still observed in the absence of microglia.