{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gratuze M"],"funding":["NIA NIH HHS","NINDS NIH HHS","NIH HHS"],"pagination":["202-219.e7"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9852006"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["111(2)"],"pubmed_abstract":["In addition to tau and Aβ pathologies, inflammation plays an important role in Alzheimer's disease (AD). Variants in APOE and TREM2 increase AD risk. ApoE4 exacerbates tau-linked neurodegeneration and inflammation in P301S tau mice and removal of microglia blocks tau-dependent neurodegeneration. Microglia adopt a heterogeneous population of transcriptomic states in response to pathology, at least some of which are dependent on TREM2. Previously, we reported that knockout (KO) of TREM2 attenuated neurodegeneration in P301S mice that express mouse Apoe. Because of the possible common pathway of ApoE and TREM2 in AD, we tested whether TREM2 KO (T2KO) would block neurodegeneration in P301S Tau mice expressing ApoE4 (TE4), similar to that observed with microglial depletion. Surprisingly, we observed exacerbated neurodegeneration and tau pathology in TE4-T2KO versus TE4 mice, despite decreased TREM2-dependent microgliosis. Our results suggest that tau pathology-dependent microgliosis, that is, TREM2-independent microgliosis, facilitates tau-mediated neurodegeneration in the presence of ApoE4."],"journal":["Neuron"],"pubmed_title":["TREM2-independent microgliosis promotes tau-mediated neurodegeneration in the presence of ApoE4."],"pmcid":["PMC9852006"],"funding_grant_id":["U01 AG061356","R01 AG015819","R01 AG057777","RF1 AG061060","R01 AG074012","R01 AG044546","RF1 NS090934","P30 AG066444","S10 OD026929","R56 AG067764","R01 AG030146","U19 AG069701","RF1 AG057473","S10 OD021629","T32 AG058518","P30 AG010161","RF1 AG058501","R01 AG056511","RF1 AG053303","U01 AG072464","P01 AG026276","U01 AG032984","R01 AG017917","RF1 AG047644","P01 AG003991"],"pubmed_authors":["Schlachetzki JCM","Rodriguez L","Jain N","D'Oliveira Albanus R","Colonna M","Holtzman DM","Ulrich JD","Harari O","Glass CK","Lee C","Mansel C","Manis M","Gratuze M","Kipnis M","Pasillas MP","O'Brien S","Novotny B","Brase L"],"additional_accession":[]},"is_claimable":false,"name":"TREM2-independent microgliosis promotes tau-mediated neurodegeneration in the presence of ApoE4.","description":"In addition to tau and Aβ pathologies, inflammation plays an important role in Alzheimer's disease (AD). Variants in APOE and TREM2 increase AD risk. ApoE4 exacerbates tau-linked neurodegeneration and inflammation in P301S tau mice and removal of microglia blocks tau-dependent neurodegeneration. Microglia adopt a heterogeneous population of transcriptomic states in response to pathology, at least some of which are dependent on TREM2. Previously, we reported that knockout (KO) of TREM2 attenuated neurodegeneration in P301S mice that express mouse Apoe. Because of the possible common pathway of ApoE and TREM2 in AD, we tested whether TREM2 KO (T2KO) would block neurodegeneration in P301S Tau mice expressing ApoE4 (TE4), similar to that observed with microglial depletion. Surprisingly, we observed exacerbated neurodegeneration and tau pathology in TE4-T2KO versus TE4 mice, despite decreased TREM2-dependent microgliosis. Our results suggest that tau pathology-dependent microgliosis, that is, TREM2-independent microgliosis, facilitates tau-mediated neurodegeneration in the presence of ApoE4.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2026-05-28T21:55:10.354Z","creation":"2025-04-03T23:50:48.399Z"},"accession":"S-EPMC9852006","cross_references":{"pubmed":["36368315"],"doi":["10.1016/j.neuron.2022.10.022"]}}