Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia.
Dan XiaSteve LianoglouThomas SandmannMeredith CalvertJung H SuhElliot ThomsenJason DugasMichelle E PizzoSarah L DeVosTimothy K EarrChia-Ching LinSonnet DavisConnie HaAmy Wing-Sze LeungHoang NguyenRoni ChauErnie YulyaningsihIsabel LopezHilda SolanoyShababa T MasoudChun-Chi LiangKarin LinGiuseppe AstaritaNathalie KhouryJoy Yu ZucheroRobert G ThorneKevin ShenStephanie MillerJorge J PalopDylan GarceauMichael SasnerJennifer D WhitesellJulie A HarrisSelina HummelJohannes GnörichKarin WindLea KunzeArtem ZatcepinMatthias BrendelMichael WillemChristian HaassDaniel BarnettTill S ZimmerAnna G OrrKimberly Scearce-LevieJoseph W LewcockGilbert Di PaoloPascal E SanchezPublished in: Molecular neurodegeneration (2022)
Our findings demonstrate that fibrillar Aβ in microglia is associated with lipid dyshomeostasis consistent with lysosomal dysfunction and foam cell phenotypes as well as profound immuno-metabolic perturbations, opening new avenues to further investigate metabolic pathways at play in microglia responding to AD-relevant pathogenesis. The in-depth characterization of pathological hallmarks of AD in this novel and open-access mouse model should serve as a resource for the scientific community to investigate disease-relevant biology.