Anti-human TREM2 induces microglia proliferation and reduces pathology in an Alzheimer’s disease model
TREM2 is a receptor for lipids expressed in microglia. The R47H variant of human TREM2 impairs ligand binding and increases Alzheimer’s disease (AD) risk. In mouse models of amyloid β (Aβ) accumulation, defective TREM2 function affects microglial response to Aβ plaques, exacerbating tissue damage, w...
Saved in:
| Published in | The Journal of experimental medicine Vol. 217; no. 9 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Rockefeller University Press
07.09.2020
|
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | TREM2 is a receptor for lipids expressed in microglia. The R47H variant of human TREM2 impairs ligand binding and increases Alzheimer’s disease (AD) risk. In mouse models of amyloid β (Aβ) accumulation, defective TREM2 function affects microglial response to Aβ plaques, exacerbating tissue damage, whereas TREM2 overexpression attenuates pathology. Thus, AD may benefit from TREM2 activation. Here, we examined the impact of an anti-human TREM2 agonistic mAb, AL002c, in a mouse AD model expressing either the common variant (CV) or the R47H variant of TREM2. Single-cell RNA-seq of microglia after acute systemic administration of AL002c showed induction of proliferation in both CV- and R47H-transgenic mice. Prolonged administration of AL002c reduced filamentous plaques and neurite dystrophy, impacted behavior, and tempered microglial inflammatory response. We further showed that a variant of AL002c is safe and well tolerated in a first-in-human phase I clinical trial and engages TREM2 based on cerebrospinal fluid biomarkers. We conclude that AL002 is a promising candidate for AD therapy. |
|---|---|
| AbstractList | TREM2 is a receptor for lipids expressed in microglia. The R47H variant of human TREM2 impairs ligand binding and increases Alzheimer's disease (AD) risk. In mouse models of amyloid β (Aβ) accumulation, defective TREM2 function affects microglial response to Aβ plaques, exacerbating tissue damage, whereas TREM2 overexpression attenuates pathology. Thus, AD may benefit from TREM2 activation. Here, we examined the impact of an anti-human TREM2 agonistic mAb, AL002c, in a mouse AD model expressing either the common variant (CV) or the R47H variant of TREM2. Single-cell RNA-seq of microglia after acute systemic administration of AL002c showed induction of proliferation in both CV- and R47H-transgenic mice. Prolonged administration of AL002c reduced filamentous plaques and neurite dystrophy, impacted behavior, and tempered microglial inflammatory response. We further showed that a variant of AL002c is safe and well tolerated in a first-in-human phase I clinical trial and engages TREM2 based on cerebrospinal fluid biomarkers. We conclude that AL002 is a promising candidate for AD therapy. Wang et al. demonstrate that a mAb specific for the human microglial receptor TREM2 induces microglia proliferation, ameliorates Aβ-induced pathology in a mouse model of Alzheimer’s disease, and can be given safely in a first-in-human phase I clinical trial. TREM2 is a receptor for lipids expressed in microglia. The R47H variant of human TREM2 impairs ligand binding and increases Alzheimer’s disease (AD) risk. In mouse models of amyloid β (Aβ) accumulation, defective TREM2 function affects microglial response to Aβ plaques, exacerbating tissue damage, whereas TREM2 overexpression attenuates pathology. Thus, AD may benefit from TREM2 activation. Here, we examined the impact of an anti-human TREM2 agonistic mAb, AL002c, in a mouse AD model expressing either the common variant (CV) or the R47H variant of TREM2. Single-cell RNA-seq of microglia after acute systemic administration of AL002c showed induction of proliferation in both CV- and R47H-transgenic mice. Prolonged administration of AL002c reduced filamentous plaques and neurite dystrophy, impacted behavior, and tempered microglial inflammatory response. We further showed that a variant of AL002c is safe and well tolerated in a first-in-human phase I clinical trial and engages TREM2 based on cerebrospinal fluid biomarkers. We conclude that AL002 is a promising candidate for AD therapy. TREM2 is a receptor for lipids expressed in microglia. The R47H variant of human TREM2 impairs ligand binding and increases Alzheimer's disease (AD) risk. In mouse models of amyloid β (Aβ) accumulation, defective TREM2 function affects microglial response to Aβ plaques, exacerbating tissue damage, whereas TREM2 overexpression attenuates pathology. Thus, AD may benefit from TREM2 activation. Here, we examined the impact of an anti-human TREM2 agonistic mAb, AL002c, in a mouse AD model expressing either the common variant (CV) or the R47H variant of TREM2. Single-cell RNA-seq of microglia after acute systemic administration of AL002c showed induction of proliferation in both CV- and R47H-transgenic mice. Prolonged administration of AL002c reduced filamentous plaques and neurite dystrophy, impacted behavior, and tempered microglial inflammatory response. We further showed that a variant of AL002c is safe and well tolerated in a first-in-human phase I clinical trial and engages TREM2 based on cerebrospinal fluid biomarkers. We conclude that AL002 is a promising candidate for AD therapy.TREM2 is a receptor for lipids expressed in microglia. The R47H variant of human TREM2 impairs ligand binding and increases Alzheimer's disease (AD) risk. In mouse models of amyloid β (Aβ) accumulation, defective TREM2 function affects microglial response to Aβ plaques, exacerbating tissue damage, whereas TREM2 overexpression attenuates pathology. Thus, AD may benefit from TREM2 activation. Here, we examined the impact of an anti-human TREM2 agonistic mAb, AL002c, in a mouse AD model expressing either the common variant (CV) or the R47H variant of TREM2. Single-cell RNA-seq of microglia after acute systemic administration of AL002c showed induction of proliferation in both CV- and R47H-transgenic mice. Prolonged administration of AL002c reduced filamentous plaques and neurite dystrophy, impacted behavior, and tempered microglial inflammatory response. We further showed that a variant of AL002c is safe and well tolerated in a first-in-human phase I clinical trial and engages TREM2 based on cerebrospinal fluid biomarkers. We conclude that AL002 is a promising candidate for AD therapy. |
| Author | Ward, Michael Gilfillan, Susan Yuede, Carla M. Ibrahim, Adiljan Kong, Philip Salazar, Santiago Viveros Rhinn, Hervé Mustafa, Meer Schwabe, Tina Paul, Robert Colonna, Marco Rosenthal, Arnon Tassi, Ilaria Long, Hua Siddiqui, Omer Wang, Shoutang |
| AuthorAffiliation | 1 Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 2 Alector LLC, South San Francisco, CA 3 Department of Psychiatry and Neurology, Washington University School of Medicine, St Louis, MO |
| AuthorAffiliation_xml | – name: 3 Department of Psychiatry and Neurology, Washington University School of Medicine, St Louis, MO – name: 1 Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO – name: 2 Alector LLC, South San Francisco, CA |
| Author_xml | – sequence: 1 givenname: Shoutang orcidid: 0000-0003-1049-9127 surname: Wang fullname: Wang, Shoutang – sequence: 2 givenname: Meer orcidid: 0000-0002-2638-9523 surname: Mustafa fullname: Mustafa, Meer – sequence: 3 givenname: Carla M. surname: Yuede fullname: Yuede, Carla M. – sequence: 4 givenname: Santiago Viveros surname: Salazar fullname: Salazar, Santiago Viveros – sequence: 5 givenname: Philip surname: Kong fullname: Kong, Philip – sequence: 6 givenname: Hua surname: Long fullname: Long, Hua – sequence: 7 givenname: Michael surname: Ward fullname: Ward, Michael – sequence: 8 givenname: Omer surname: Siddiqui fullname: Siddiqui, Omer – sequence: 9 givenname: Robert surname: Paul fullname: Paul, Robert – sequence: 10 givenname: Susan orcidid: 0000-0003-1672-0996 surname: Gilfillan fullname: Gilfillan, Susan – sequence: 11 givenname: Adiljan surname: Ibrahim fullname: Ibrahim, Adiljan – sequence: 12 givenname: Hervé surname: Rhinn fullname: Rhinn, Hervé – sequence: 13 givenname: Ilaria surname: Tassi fullname: Tassi, Ilaria – sequence: 14 givenname: Arnon surname: Rosenthal fullname: Rosenthal, Arnon – sequence: 15 givenname: Tina surname: Schwabe fullname: Schwabe, Tina – sequence: 16 givenname: Marco orcidid: 0000-0001-5222-4987 surname: Colonna fullname: Colonna, Marco |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32579671$$D View this record in MEDLINE/PubMed |
| BookMark | eNptkc1uFDEQhC0URDYLN87IRw5M8O_Ye0FaReFHCkJC4Wx5xj07jjz2Ys9ECideg9fjSXDYJALEqQ_1dXWr6gQdxRQBoeeUnFKixesrmE4ZYYQoLR-hFZWCNBvJ9RFaEcJYQ6tyjE5KuSKECiHbJ-iYM6k2raIrNG7j7JtxmWzEl5_PPzLso1t6KHjyfU674C3e5xT8ANnOPkVso8MZDszezmMKaXdTt6qAt-HbCH6C_PP7j4KdL2AL4Ck5CE_R48GGAs_u5hp9eXt-efa-ufj07sPZ9qLphSRzw9uB2NY56vpW6ZZ2HeW9boGBlJp33UYyDkoO3cBlBS2xgm06zYlTgxsY52v05uC7X7oJXA9xzjaYffaTzTcmWW_-VqIfzS5dGyWUVpxUg5d3Bjl9XaDMZvKlhxBshLQUwwRVXIvbd9boxZ-3Ho7cx1uBVwegRllKhuEBocTctmdqe-a-vYqzf_Dez79Tr5_68P-lX452oDY |
| CitedBy_id | crossref_primary_10_3892_etm_2023_11904 crossref_primary_10_1186_s40478_021_01204_8 crossref_primary_10_1186_s12974_025_03420_8 crossref_primary_10_1016_j_str_2021_06_010 crossref_primary_10_1177_17590914211051908 crossref_primary_10_1177_03946320231184988 crossref_primary_10_1093_procel_pwae026 crossref_primary_10_1038_s41380_023_02017_y crossref_primary_10_3389_fncel_2021_749587 crossref_primary_10_1002_alz_14477 crossref_primary_10_3389_fimmu_2025_1462508 crossref_primary_10_1016_j_tins_2020_08_002 crossref_primary_10_1177_10738584211040786 crossref_primary_10_1186_s13024_024_00712_0 crossref_primary_10_1038_s41582_025_01062_1 crossref_primary_10_1016_j_neuroscience_2024_11_078 crossref_primary_10_1016_j_stem_2023_07_006 crossref_primary_10_1186_s12974_024_03163_y crossref_primary_10_1186_s13024_020_00415_2 crossref_primary_10_1111_jnc_15538 crossref_primary_10_1002_alz_13020 crossref_primary_10_1016_j_it_2025_02_011 crossref_primary_10_1038_s41392_023_01588_0 crossref_primary_10_1093_brain_awad321 crossref_primary_10_1084_jem_20202717 crossref_primary_10_1186_s13195_024_01470_3 crossref_primary_10_3389_fnagi_2023_1264448 crossref_primary_10_1016_j_expneurol_2024_115071 crossref_primary_10_1016_j_ccell_2023_09_001 crossref_primary_10_1016_S1474_4422_23_00247_8 crossref_primary_10_1038_s42255_021_00341_7 crossref_primary_10_1016_j_conb_2021_09_003 crossref_primary_10_1016_j_intimp_2024_113286 crossref_primary_10_1038_s41573_023_00823_1 crossref_primary_10_1126_scitranslmed_abq0095 crossref_primary_10_1177_11795735221123896 crossref_primary_10_1038_s41392_024_01911_3 crossref_primary_10_1007_s12031_022_01965_4 crossref_primary_10_1016_j_drudis_2024_104093 crossref_primary_10_1016_j_biopha_2024_117235 crossref_primary_10_4254_wjh_v17_i2_102328 crossref_primary_10_1038_s41467_023_42814_1 crossref_primary_10_3389_fnagi_2021_834697 crossref_primary_10_3390_ijms252211941 crossref_primary_10_1126_scitranslmed_adj9052 crossref_primary_10_1016_j_biopha_2023_115218 crossref_primary_10_1038_s41590_023_01475_4 crossref_primary_10_2174_1567205020666230203112351 crossref_primary_10_3389_fcell_2022_999024 crossref_primary_10_1038_s41467_020_19227_5 crossref_primary_10_1186_s13024_024_00734_8 crossref_primary_10_1002_alz_13921 crossref_primary_10_1146_annurev_immunol_093019_111748 crossref_primary_10_1016_j_taap_2024_117107 crossref_primary_10_31083_j_jin2203072 crossref_primary_10_1038_s41593_022_01240_0 crossref_primary_10_3390_ph13110394 crossref_primary_10_4103_1673_5374_371360 crossref_primary_10_1186_s13195_024_01599_1 crossref_primary_10_1073_pnas_2017742118 crossref_primary_10_1007_s00018_024_05298_w crossref_primary_10_3389_fphar_2023_1196413 crossref_primary_10_1039_D3CP01083J crossref_primary_10_1084_jem_20222105 crossref_primary_10_1007_s00018_022_04536_3 crossref_primary_10_3233_JAD_221064 crossref_primary_10_1212_NXG_0000000000000574 crossref_primary_10_1186_s40364_024_00675_w crossref_primary_10_1126_sciadv_adf5808 crossref_primary_10_1161_ATVBAHA_124_320797 crossref_primary_10_3390_vaccines10060943 crossref_primary_10_1186_s12974_025_03346_1 crossref_primary_10_4103_1673_5374_373670 crossref_primary_10_1016_j_stem_2022_01_007 crossref_primary_10_1007_s44194_024_00035_8 crossref_primary_10_1002_glia_24602 crossref_primary_10_3389_fnins_2021_742065 crossref_primary_10_1080_13543776_2021_1883587 crossref_primary_10_1186_s12974_022_02580_1 crossref_primary_10_7554_eLife_73021 crossref_primary_10_1007_s00415_021_10790_5 crossref_primary_10_1177_10738584211024531 crossref_primary_10_26508_lsa_202403080 crossref_primary_10_3390_diagnostics12040796 crossref_primary_10_1038_s41421_024_00666_z crossref_primary_10_1016_j_celrep_2023_112629 crossref_primary_10_1186_s13195_024_01646_x crossref_primary_10_1007_s12035_022_03100_1 crossref_primary_10_1016_j_biopha_2022_113412 crossref_primary_10_1002_glia_24047 crossref_primary_10_1016_j_nbd_2021_105398 crossref_primary_10_31083_j_jin2203058 crossref_primary_10_1038_s41591_023_02505_2 crossref_primary_10_1039_D4SC06762B crossref_primary_10_1016_j_drudis_2024_103974 crossref_primary_10_26508_lsa_202402796 crossref_primary_10_3389_fimmu_2020_617860 crossref_primary_10_1016_j_neurobiolaging_2022_06_013 crossref_primary_10_1016_j_it_2024_08_001 crossref_primary_10_1186_s12974_022_02671_z crossref_primary_10_1073_pnas_2218915120 crossref_primary_10_1093_hmg_ddae115 crossref_primary_10_1155_2021_4793517 crossref_primary_10_3390_cells11121925 crossref_primary_10_1016_j_neuron_2021_02_010 crossref_primary_10_1002_brb3_70455 crossref_primary_10_3389_fnsyn_2021_773590 crossref_primary_10_3389_fneur_2024_1515252 crossref_primary_10_1111_cns_14856 crossref_primary_10_3390_ijms22062805 crossref_primary_10_2147_ITT_S455881 crossref_primary_10_3390_ijms25010016 crossref_primary_10_1002_trc2_12350 crossref_primary_10_1007_s00018_022_04614_6 crossref_primary_10_1177_10738584241254118 crossref_primary_10_1007_s00415_024_12779_2 crossref_primary_10_1186_s13024_023_00599_3 crossref_primary_10_3390_pharmaceutics17010013 crossref_primary_10_3390_biomedicines11123232 crossref_primary_10_1016_j_pnpbp_2024_111069 crossref_primary_10_3233_JAD_231159 crossref_primary_10_1016_j_semcdb_2022_03_032 crossref_primary_10_1084_jem_20220654 crossref_primary_10_1186_s13024_021_00443_6 crossref_primary_10_1016_j_chemphyslip_2024_105449 crossref_primary_10_1186_s41983_021_00420_2 crossref_primary_10_1002_cbic_202400224 crossref_primary_10_1084_jem_20212479 crossref_primary_10_3389_fimmu_2021_795036 crossref_primary_10_3390_cells12111549 crossref_primary_10_3389_fnagi_2022_1056067 crossref_primary_10_3390_biom14080918 crossref_primary_10_4103_NRR_NRR_D_23_01401 crossref_primary_10_1523_ENEURO_0260_24_2024 crossref_primary_10_1016_j_lfs_2024_123089 crossref_primary_10_1016_j_envres_2024_118602 crossref_primary_10_1016_j_arr_2024_102192 crossref_primary_10_3389_fimmu_2022_969127 crossref_primary_10_1084_jem_20221850 crossref_primary_10_1615_CritRevImmunol_2024054889 crossref_primary_10_7554_eLife_79830 crossref_primary_10_3389_fnins_2024_1420601 crossref_primary_10_3390_biology13020087 crossref_primary_10_3143_geriatrics_57_374 crossref_primary_10_1002_glia_24252 crossref_primary_10_1007_s12035_022_03133_6 crossref_primary_10_3389_fddev_2023_1227816 crossref_primary_10_1111_ejn_16541 crossref_primary_10_1038_s41577_024_01104_7 crossref_primary_10_1186_s13024_022_00550_y crossref_primary_10_1007_s12975_024_01236_x crossref_primary_10_3390_cells14030168 crossref_primary_10_1073_pnas_2426786122 crossref_primary_10_3390_ijms24010013 crossref_primary_10_1016_j_neuron_2020_09_029 crossref_primary_10_3390_ijms231810572 crossref_primary_10_1002_advs_202307245 crossref_primary_10_1007_s40265_023_01938_w crossref_primary_10_1111_imm_13300 crossref_primary_10_1016_j_cellimm_2023_104743 crossref_primary_10_1038_s44161_023_00354_3 crossref_primary_10_1021_acsnano_3c13150 crossref_primary_10_1002_glia_23953 crossref_primary_10_1002_glia_24007 crossref_primary_10_1016_j_hlife_2024_11_006 crossref_primary_10_1111_ejn_15914 crossref_primary_10_3389_fimmu_2022_856376 crossref_primary_10_3390_biomedicines9101449 crossref_primary_10_3389_fphar_2023_1125982 crossref_primary_10_1186_s40035_022_00292_3 crossref_primary_10_1016_j_nbd_2022_105630 crossref_primary_10_1111_cns_14129 crossref_primary_10_1080_19420862_2022_2107971 crossref_primary_10_1002_alz_12577 crossref_primary_10_1016_j_drudis_2023_103652 crossref_primary_10_1016_j_arr_2024_102411 crossref_primary_10_1126_sciadv_ade3559 crossref_primary_10_1186_s13024_022_00588_y crossref_primary_10_1016_j_celrep_2022_110883 crossref_primary_10_3233_JAD_230179 crossref_primary_10_1002_dneu_22864 crossref_primary_10_1016_j_jneuroim_2024_578342 crossref_primary_10_1016_j_intimp_2024_113446 crossref_primary_10_1186_s13024_021_00436_5 crossref_primary_10_1126_scitranslmed_abl7634 crossref_primary_10_1038_s41577_023_00837_1 crossref_primary_10_1002_ctm2_1200 crossref_primary_10_3390_jcm13113098 crossref_primary_10_1002_alz_12342 crossref_primary_10_1186_s12974_023_02750_9 crossref_primary_10_1002_alz_14402 crossref_primary_10_1097_MD_0000000000038898 crossref_primary_10_3389_fimmu_2021_676255 crossref_primary_10_1016_j_neuropharm_2024_110020 crossref_primary_10_3389_fnins_2024_1440334 crossref_primary_10_1002_ptr_7848 crossref_primary_10_1016_j_isci_2023_106375 crossref_primary_10_3390_ijms251810041 crossref_primary_10_1016_j_nbd_2020_105172 crossref_primary_10_1002_glia_24461 crossref_primary_10_3390_cells13171426 crossref_primary_10_7554_eLife_90695_3 crossref_primary_10_3389_fnagi_2023_1201982 crossref_primary_10_1111_febs_16638 crossref_primary_10_1073_pnas_2100356118 crossref_primary_10_1038_s41591_025_03574_1 crossref_primary_10_1002_2211_5463_13300 crossref_primary_10_3389_fnagi_2023_1259012 crossref_primary_10_1002_glia_24456 crossref_primary_10_1038_s41392_023_01486_5 crossref_primary_10_1016_j_biopha_2023_115962 crossref_primary_10_1128_mbio_01456_22 crossref_primary_10_3390_ijms241511922 crossref_primary_10_1016_j_neuint_2020_104878 crossref_primary_10_1038_s41593_023_01265_z crossref_primary_10_2147_CIA_S357558 crossref_primary_10_3389_fnins_2023_1308345 crossref_primary_10_1016_j_pneurobio_2022_102298 crossref_primary_10_1016_j_mcn_2024_103917 crossref_primary_10_1007_s00401_023_02564_2 crossref_primary_10_3389_fnagi_2022_998049 crossref_primary_10_7554_eLife_83451 crossref_primary_10_14283_jpad_2023_111 crossref_primary_10_1038_s41598_024_52311_0 crossref_primary_10_1177_10738584211070273 crossref_primary_10_3390_biom10101439 crossref_primary_10_1016_j_ejphar_2024_176859 crossref_primary_10_1523_JNEUROSCI_2347_23_2024 crossref_primary_10_3390_molecules27134124 crossref_primary_10_3389_fnmol_2023_1183315 crossref_primary_10_1016_j_cmet_2023_03_006 crossref_primary_10_54097_hset_v54i_9763 crossref_primary_10_1016_j_drudis_2022_01_004 crossref_primary_10_1016_j_neubiorev_2025_106044 crossref_primary_10_1093_abt_tbac028 crossref_primary_10_1097_HC9_0000000000000203 crossref_primary_10_1016_j_neuroscience_2025_03_033 crossref_primary_10_1111_ejn_15609 crossref_primary_10_1007_s12035_022_03094_w crossref_primary_10_1515_revneuro_2022_0087 crossref_primary_10_3390_ijms22189734 crossref_primary_10_3390_medicina59061084 crossref_primary_10_3389_fneur_2024_1330874 crossref_primary_10_3390_cells11121885 crossref_primary_10_3389_fnins_2021_806260 crossref_primary_10_1111_cns_70269 crossref_primary_10_1016_j_celrep_2024_114250 crossref_primary_10_1111_jnc_15987 crossref_primary_10_1186_s13024_022_00517_z crossref_primary_10_1186_s13024_020_00402_7 crossref_primary_10_1007_s13311_023_01441_w crossref_primary_10_1016_j_nbd_2024_106505 crossref_primary_10_1016_j_cell_2022_10_007 crossref_primary_10_1007_s10787_024_01550_8 crossref_primary_10_31083_j_jin2201002 crossref_primary_10_1248_cpb_c23_00464 crossref_primary_10_1016_j_intimp_2025_114284 crossref_primary_10_3389_frdem_2024_1458038 crossref_primary_10_1016_j_drudis_2022_06_005 crossref_primary_10_1016_j_arr_2024_102595 crossref_primary_10_1016_j_arr_2024_102596 crossref_primary_10_1186_s12974_021_02309_6 crossref_primary_10_3390_antiox13060651 crossref_primary_10_1186_s13024_021_00473_0 crossref_primary_10_3390_cells10040957 crossref_primary_10_3390_ijms231810722 crossref_primary_10_3390_neurolint15030053 crossref_primary_10_1097_WCO_0000000000000911 crossref_primary_10_1186_s12974_020_02024_8 crossref_primary_10_1177_17590914231197523 crossref_primary_10_3390_molecules26195946 crossref_primary_10_1038_s42003_023_04998_6 crossref_primary_10_3390_ijms21239036 crossref_primary_10_1016_j_cell_2022_09_033 crossref_primary_10_1016_j_brainres_2024_149245 crossref_primary_10_1084_jem_20231363 crossref_primary_10_4103_1673_5374_353484 crossref_primary_10_1165_rcmb_2020_0521OC crossref_primary_10_7554_eLife_90695 crossref_primary_10_3389_fnagi_2024_1420731 crossref_primary_10_4103_1673_5374_385847 crossref_primary_10_1253_jjcsc_31_0_11 crossref_primary_10_3390_biom14070833 |
| Cites_doi | 10.1126/science.1110647 10.15252/emmm.201911227 10.1016/j.cell.2017.05.018 10.1172/JCI90606 10.1084/jem.20151948 10.1038/s41593-019-0393-4 10.1016/j.biopsych.2014.05.006 10.1101/719930 10.1111/imr.12350 10.1038/ng.2802 10.1038/nn1472 10.1093/brain/awq056 10.1038/s41586-019-1195-2 10.1038/ni.1744 10.1371/journal.pone.0066024 10.1016/j.cell.2019.09.001 10.15252/emmm.201707672 10.1016/j.jalz.2016.07.004 10.1093/brain/awn217 10.1016/j.cell.2017.07.023 10.1016/j.neuron.2016.05.003 10.1038/s41591-019-0695-9 10.1038/nn2015 10.1101/cshperspect.a006338 10.1016/j.neulet.2017.09.034 10.1007/s12035-016-0167-x 10.1126/science.aad0501 10.1016/j.nbd.2009.06.002 10.1056/NEJMoa1211851 10.1074/jbc.RA118.001848 10.1074/jbc.M113.517540 10.1084/jem.20171529 10.1016/j.celrep.2017.09.039 10.1056/NEJMoa1211103 10.1523/JNEUROSCI.1202-06.2006 10.1016/j.celrep.2019.03.099 10.1523/JNEUROSCI.23-34-10879.2003 10.1016/j.cell.2015.01.049 10.1016/j.neuron.2018.02.002 10.1016/j.brainres.2017.12.028 10.1038/nbt.4096 |
| ContentType | Journal Article |
| Copyright | 2020 Wang et al. 2020 Wang et al. 2020 |
| Copyright_xml | – notice: 2020 Wang et al. – notice: 2020 Wang et al. 2020 |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM 7X8 5PM |
| DOI | 10.1084/jem.20200785 |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic PubMed Central (Full Participant titles) |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE MEDLINE - Academic CrossRef |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| DocumentTitleAlternate | A mAb targeting human TREM2 in Alzheimer’s disease |
| EISSN | 1540-9538 |
| ExternalDocumentID | PMC7478730 32579671 10_1084_jem_20200785 |
| Genre | Clinical Trial, Phase I Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NIA NIH HHS grantid: R21 AG059176 – fundername: NIA NIH HHS grantid: RF1 AG059082 – fundername: ; – fundername: ; grantid: RF1AG05148501; R21 AG059176; RF1 AG059082 |
| GroupedDBID | --- -~X 18M 29K 2WC 36B 4.4 53G 5GY 5RE 5VS AAYXX ABOCM ABZEH ACGFO ACNCT ACPRK ADBBV AENEX AFOSN AFRAH ALMA_UNASSIGNED_HOLDINGS AOIJS BAWUL BTFSW C45 CITATION CS3 D-I DIK DU5 E3Z EBS EMB F5P F9R GX1 H13 HYE IH2 KQ8 L7B N9A O5R O5S OK1 P2P P6G R.V RHI SJN TR2 TRP UHB W8F WOQ CGR CUY CVF ECM EIF NPM 7X8 5PM |
| ID | FETCH-LOGICAL-c450t-36f0a6dd1dc67861bb13c86e2e5583bb9523e75fbf350a6a0a429b830d7fdf233 |
| ISSN | 0022-1007 1540-9538 |
| IngestDate | Thu Aug 21 14:09:44 EDT 2025 Fri Jul 11 11:21:09 EDT 2025 Thu Apr 03 06:57:31 EDT 2025 Tue Jul 01 00:41:14 EDT 2025 Thu Apr 24 22:54:12 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 9 |
| Language | English |
| License | 2020 Wang et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
| LinkModel | OpenURL |
| MergedId | FETCHMERGED-LOGICAL-c450t-36f0a6dd1dc67861bb13c86e2e5583bb9523e75fbf350a6a0a429b830d7fdf233 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 S. Wang and M. Mustafa contributed equally to this paper. Disclosures: M. Mustafa, S.V. Salazar, P. Kong, H. Long, M. Ward, O. Siddiqui, R. Paul, A. Ibrahim, H. Rhinn, I. Tassi, A. Rosenthal, and T. Schwabe reported "other" from Alector, Inc. during the conduct of the study. The authors are employees of Alector LLC and may have an equity interest in Alector, Inc. Alector and AbbVie are parties to an agreement relating to the development and commercialization of AL002. M. Colonna reported "other" from Alector and grants from Alector, Amgen, and Ono during the conduct of the study. In addition, Alector LLC has pending patent applications and M. Colonna has a patent to TREM2 pending. No other disclosures were reported. |
| ORCID | 0000-0003-1672-0996 0000-0001-5222-4987 0000-0002-2638-9523 0000-0003-1049-9127 |
| OpenAccessLink | https://pubmed.ncbi.nlm.nih.gov/PMC7478730 |
| PMID | 32579671 |
| PQID | 2417384558 |
| PQPubID | 23479 |
| ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_7478730 proquest_miscellaneous_2417384558 pubmed_primary_32579671 crossref_primary_10_1084_jem_20200785 crossref_citationtrail_10_1084_jem_20200785 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 2020-09-07 |
| PublicationDateYYYYMMDD | 2020-09-07 |
| PublicationDate_xml | – month: 09 year: 2020 text: 2020-09-07 day: 07 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | The Journal of experimental medicine |
| PublicationTitleAlternate | J Exp Med |
| PublicationYear | 2020 |
| Publisher | Rockefeller University Press |
| Publisher_xml | – name: Rockefeller University Press |
| References | Van Hove (2023072812444460100_bib34) 2019; 22 Zhou (2023072812444460100_bib41) 2020; 26 Mucke (2023072812444460100_bib20) 2012; 2 Braun (2023072812444460100_bib1) 2019; 1702 Cheng (2023072812444460100_bib5) 2018; 293 Schlepckow (2023072812444460100_bib27) 2017; 9 Lombardo (2023072812444460100_bib15) 2003; 23 Yuede (2023072812444460100_bib40) 2009; 35 Song (2023072812444460100_bib30) 2017; 13 Oakley (2023072812444460100_bib22) 2006; 26 Guerreiro (2023072812444460100_bib8) 2013; 368 Mathys (2023072812444460100_bib18) 2019; 570 Sala Frigerio (2023072812444460100_bib25) 2019; 27 Piccio (2023072812444460100_bib24) 2008; 131 Wang (2023072812444460100_bib36) 2016; 213 Wang (2023072812444460100_bib35) 2015; 160 Mildner (2023072812444460100_bib19) 2007; 10 Keren-Shaul (2023072812444460100_bib12) 2017; 169 Ulland (2023072812444460100_bib33) 2017; 170 Song (2023072812444460100_bib31) 2018; 215 2023072812444460100_bib4 Davalos (2023072812444460100_bib6) 2005; 8 Sarlus (2023072812444460100_bib26) 2017; 127 Wozniak (2023072812444460100_bib37) 2013; 8 Wunderlich (2023072812444460100_bib38) 2013; 288 Mathys (2023072812444460100_bib17) 2017; 21 Tirosh (2023072812444460100_bib32) 2016; 352 Nimmerjahn (2023072812444460100_bib21) 2005; 308 Karch (2023072812444460100_bib11) 2015; 77 Bruhns (2023072812444460100_bib2) 2015; 268 Otero (2023072812444460100_bib23) 2009; 10 Schlepckow (2023072812444460100_bib28) 2020; 12 Feuerbach (2023072812444460100_bib7) 2017; 660 Jonsson (2023072812444460100_bib10) 2013; 368 Lambert (2023072812444460100_bib13) 2013; 45 Hüttenrauch (2023072812444460100_bib9) 2017; 54 Yuan (2023072812444460100_bib39) 2016; 90 Lee (2023072812444460100_bib14) 2018; 97 Long (2023072812444460100_bib16) 2019; 179 Serrano-Pozo (2023072812444460100_bib29) 2010; 133 Butler (2023072812444460100_bib3) 2018; 36 |
| References_xml | – volume: 308 start-page: 1314 year: 2005 ident: 2023072812444460100_bib21 article-title: Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo publication-title: Science doi: 10.1126/science.1110647 – volume: 12 year: 2020 ident: 2023072812444460100_bib28 article-title: Enhancing protective microglial activities with a dual function TREM2 antibody to the stalk region publication-title: EMBO Mol. Med doi: 10.15252/emmm.201911227 – volume: 169 start-page: 1276 year: 2017 ident: 2023072812444460100_bib12 article-title: A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease publication-title: Cell doi: 10.1016/j.cell.2017.05.018 – volume: 127 start-page: 3240 year: 2017 ident: 2023072812444460100_bib26 article-title: Microglia in Alzheimer’s disease publication-title: J. Clin. Invest doi: 10.1172/JCI90606 – volume: 213 start-page: 667 year: 2016 ident: 2023072812444460100_bib36 article-title: TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques publication-title: J. Exp. Med doi: 10.1084/jem.20151948 – volume: 22 start-page: 1021 year: 2019 ident: 2023072812444460100_bib34 article-title: A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment publication-title: Nat. Neurosci doi: 10.1038/s41593-019-0393-4 – volume: 77 start-page: 43 year: 2015 ident: 2023072812444460100_bib11 article-title: Alzheimer’s disease risk genes and mechanisms of disease pathogenesis publication-title: Biol. Psychiatry doi: 10.1016/j.biopsych.2014.05.006 – ident: 2023072812444460100_bib4 doi: 10.1101/719930 – volume: 268 start-page: 25 year: 2015 ident: 2023072812444460100_bib2 article-title: Mouse and human FcR effector functions publication-title: Immunol. Rev doi: 10.1111/imr.12350 – volume: 45 start-page: 1452 year: 2013 ident: 2023072812444460100_bib13 article-title: Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease publication-title: Nat. Genet doi: 10.1038/ng.2802 – volume: 8 start-page: 752 year: 2005 ident: 2023072812444460100_bib6 article-title: ATP mediates rapid microglial response to local brain injury in vivo publication-title: Nat. Neurosci doi: 10.1038/nn1472 – volume: 133 start-page: 1312 year: 2010 ident: 2023072812444460100_bib29 article-title: Beneficial effect of human anti-amyloid-β active immunization on neurite morphology and tau pathology publication-title: Brain doi: 10.1093/brain/awq056 – volume: 570 start-page: 332 year: 2019 ident: 2023072812444460100_bib18 article-title: Single-cell transcriptomic analysis of Alzheimer’s disease publication-title: Nature doi: 10.1038/s41586-019-1195-2 – volume: 10 start-page: 734 year: 2009 ident: 2023072812444460100_bib23 article-title: Macrophage colony-stimulating factor induces the proliferation and survival of macrophages via a pathway involving DAP12 and β-catenin publication-title: Nat. Immunol doi: 10.1038/ni.1744 – volume: 8 year: 2013 ident: 2023072812444460100_bib37 article-title: Motivational disturbances and effects of L-dopa administration in neurofibromatosis-1 model mice publication-title: PLoS One doi: 10.1371/journal.pone.0066024 – volume: 179 start-page: 312 year: 2019 ident: 2023072812444460100_bib16 article-title: Alzheimer Disease: An Update on Pathobiology and Treatment Strategies publication-title: Cell doi: 10.1016/j.cell.2019.09.001 – volume: 9 start-page: 1356 year: 2017 ident: 2023072812444460100_bib27 article-title: An Alzheimer-associated TREM2 variant occurs at the ADAM cleavage site and affects shedding and phagocytic function publication-title: EMBO Mol. Med doi: 10.15252/emmm.201707672 – volume: 13 start-page: 381 year: 2017 ident: 2023072812444460100_bib30 article-title: Alzheimer’s disease-associated TREM2 variants exhibit either decreased or increased ligand-dependent activation publication-title: Alzheimers Dement doi: 10.1016/j.jalz.2016.07.004 – volume: 131 start-page: 3081 year: 2008 ident: 2023072812444460100_bib24 article-title: Identification of soluble TREM-2 in the cerebrospinal fluid and its association with multiple sclerosis and CNS inflammation publication-title: Brain doi: 10.1093/brain/awn217 – volume: 170 start-page: 649 year: 2017 ident: 2023072812444460100_bib33 article-title: TREM2 Maintains Microglial Metabolic Fitness in Alzheimer’s Disease publication-title: Cell doi: 10.1016/j.cell.2017.07.023 – volume: 90 start-page: 724 year: 2016 ident: 2023072812444460100_bib39 article-title: TREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy publication-title: Neuron doi: 10.1016/j.neuron.2016.05.003 – volume: 26 start-page: 131 year: 2020 ident: 2023072812444460100_bib41 article-title: Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease publication-title: Nat. Med doi: 10.1038/s41591-019-0695-9 – volume: 10 start-page: 1544 year: 2007 ident: 2023072812444460100_bib19 article-title: Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions publication-title: Nat. Neurosci doi: 10.1038/nn2015 – volume: 2 year: 2012 ident: 2023072812444460100_bib20 article-title: Neurotoxicity of amyloid β-protein: synaptic and network dysfunction publication-title: Cold Spring Harb. Perspect. Med doi: 10.1101/cshperspect.a006338 – volume: 660 start-page: 109 year: 2017 ident: 2023072812444460100_bib7 article-title: ADAM17 is the main sheddase for the generation of human triggering receptor expressed in myeloid cells (hTREM2) ectodomain and cleaves TREM2 after Histidine 157 publication-title: Neurosci. Lett doi: 10.1016/j.neulet.2017.09.034 – volume: 54 start-page: 6542 year: 2017 ident: 2023072812444460100_bib9 article-title: Limited Effects of Prolonged Environmental Enrichment on the Pathology of 5XFAD Mice publication-title: Mol. Neurobiol doi: 10.1007/s12035-016-0167-x – volume: 352 start-page: 189 year: 2016 ident: 2023072812444460100_bib32 article-title: Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq publication-title: Science doi: 10.1126/science.aad0501 – volume: 35 start-page: 426 year: 2009 ident: 2023072812444460100_bib40 article-title: Effects of voluntary and forced exercise on plaque deposition, hippocampal volume, and behavior in the Tg2576 mouse model of Alzheimer’s disease publication-title: Neurobiol. Dis doi: 10.1016/j.nbd.2009.06.002 – volume: 368 start-page: 117 year: 2013 ident: 2023072812444460100_bib8 article-title: TREM2 variants in Alzheimer’s disease publication-title: N. Engl. J. Med doi: 10.1056/NEJMoa1211851 – volume: 293 start-page: 12620 year: 2018 ident: 2023072812444460100_bib5 article-title: TREM2-activating antibodies abrogate the negative pleiotropic effects of the Alzheimer’s disease variant Trem2R47H on murine myeloid cell function publication-title: J. Biol. Chem doi: 10.1074/jbc.RA118.001848 – volume: 288 start-page: 33027 year: 2013 ident: 2023072812444460100_bib38 article-title: Sequential proteolytic processing of the triggering receptor expressed on myeloid cells-2 (TREM2) protein by ectodomain shedding and γ-secretase-dependent intramembranous cleavage publication-title: J. Biol. Chem doi: 10.1074/jbc.M113.517540 – volume: 215 start-page: 745 year: 2018 ident: 2023072812444460100_bib31 article-title: Humanized TREM2 mice reveal microglia-intrinsic and -extrinsic effects of R47H polymorphism publication-title: J. Exp. Med doi: 10.1084/jem.20171529 – volume: 21 start-page: 366 year: 2017 ident: 2023072812444460100_bib17 article-title: Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution publication-title: Cell Rep doi: 10.1016/j.celrep.2017.09.039 – volume: 368 start-page: 107 year: 2013 ident: 2023072812444460100_bib10 article-title: Variant of TREM2 associated with the risk of Alzheimer’s disease publication-title: N. Engl. J. Med doi: 10.1056/NEJMoa1211103 – volume: 26 start-page: 10129 year: 2006 ident: 2023072812444460100_bib22 article-title: Intraneuronal β-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer’s disease mutations: potential factors in amyloid plaque formation publication-title: J. Neurosci doi: 10.1523/JNEUROSCI.1202-06.2006 – volume: 27 start-page: 1293 year: 2019 ident: 2023072812444460100_bib25 article-title: The Major Risk Factors for Alzheimer’s Disease: Age, Sex, and Genes Modulate the Microglia Response to Aβ Plaques publication-title: Cell Rep doi: 10.1016/j.celrep.2019.03.099 – volume: 23 start-page: 10879 year: 2003 ident: 2023072812444460100_bib15 article-title: Amyloid-β antibody treatment leads to rapid normalization of plaque-induced neuritic alterations publication-title: J. Neurosci doi: 10.1523/JNEUROSCI.23-34-10879.2003 – volume: 160 start-page: 1061 year: 2015 ident: 2023072812444460100_bib35 article-title: TREM2 lipid sensing sustains the microglial response in an Alzheimer’s disease model publication-title: Cell doi: 10.1016/j.cell.2015.01.049 – volume: 97 start-page: 1032 year: 2018 ident: 2023072812444460100_bib14 article-title: Elevated TREM2 Gene Dosage Reprograms Microglia Responsivity and Ameliorates Pathological Phenotypes in Alzheimer’s Disease Models publication-title: Neuron doi: 10.1016/j.neuron.2018.02.002 – volume: 1702 start-page: 29 year: 2019 ident: 2023072812444460100_bib1 article-title: The locus coeruleus neuroprotective drug vindeburnol normalizes behavior in the 5xFAD transgenic mouse model of Alzheimer’s disease publication-title: Brain Res doi: 10.1016/j.brainres.2017.12.028 – volume: 36 start-page: 411 year: 2018 ident: 2023072812444460100_bib3 article-title: Integrating single-cell transcriptomic data across different conditions, technologies, and species publication-title: Nat. Biotechnol doi: 10.1038/nbt.4096 |
| SSID | ssj0014456 |
| Score | 2.6960196 |
| Snippet | TREM2 is a receptor for lipids expressed in microglia. The R47H variant of human TREM2 impairs ligand binding and increases Alzheimer’s disease (AD) risk. In... TREM2 is a receptor for lipids expressed in microglia. The R47H variant of human TREM2 impairs ligand binding and increases Alzheimer's disease (AD) risk. In... Wang et al. demonstrate that a mAb specific for the human microglial receptor TREM2 induces microglia proliferation, ameliorates Aβ-induced pathology in a... |
| SourceID | pubmedcentral proquest pubmed crossref |
| SourceType | Open Access Repository Aggregation Database Index Database Enrichment Source |
| SubjectTerms | Alzheimer Disease - cerebrospinal fluid Alzheimer Disease - pathology Alzheimer Disease - therapy Amyloid beta-Peptides - chemistry Amyloid beta-Peptides - metabolism Animals Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - pharmacokinetics Antibodies, Monoclonal - pharmacology Antibodies, Monoclonal - therapeutic use Anxiety - pathology Biomarkers - cerebrospinal fluid Blood-Brain Barrier - drug effects Blood-Brain Barrier - pathology Cell Proliferation - drug effects Disease Models, Animal Humans Membrane Glycoproteins - immunology Membrane Glycoproteins - metabolism Mice, Inbred C57BL Mice, Transgenic Microglia - drug effects Microglia - metabolism Microglia - pathology Neurites - drug effects Neurites - pathology Neuroinflammation Osteopontin - metabolism Protein Conformation Receptors, Immunologic - immunology Receptors, Immunologic - metabolism Signal Transduction Solubility |
| Title | Anti-human TREM2 induces microglia proliferation and reduces pathology in an Alzheimer’s disease model |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/32579671 https://www.proquest.com/docview/2417384558 https://pubmed.ncbi.nlm.nih.gov/PMC7478730 |
| Volume | 217 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3NbtNAEF6FIlW9IP4JBbRIcIpcbK_XP8coKqqQjFBJIZystb3bWEqdqokvOfEafRBeiCdhxrt27LRI0IsV2euf5Puyntn5ZoaQd44nWC6dzOJMBRZGlqzUdaWllOdzobgIPUxOjj_7J2fepxmfDQa_Oqqlap0eZZtb80rugirsA1wxS_Y_kG0vCjvgM-ALW0AYtv-E8bhcF5busjc9PY7dETjYFUqsLlBmd74oBOqvFqhe0TjXYnKpx2AvYl2AqcADo_FiM5cFNlMx-odo1YRvdL-crh27zSirbdlen4DdcP33Zkl6vqzAFD3fYgyWqaqN11huRcI_KqlLAU9QiTuKj9pFILEQG60H_wp8KFBB8g1lJcve2gU4qhiJCVq2ncKULxUGKK5uJEZ2J23wl1HMoV9ZZp72bIw8h92J3NVZoIax0a0vCDv08AUhsQgBLtPqfkEdrlxe1GRhLibp6u4wOwW5v8QTbDoAU-M9ct8F76TOMZ-1yiJwUeumwe1zm3wLuPWH7o0PyH5zl75RdMPT2RXsdiyg6UPywMBNx5qHj8hAlo_JfmzQfkLmWzrSmo7U0JG2dKQ9OlKgIzV0pC0d4Sw4QFs6_v55vaKGiLQm4lNy9vF4OjmxTCMPK_O4vbaYr2zh57mTZ2Ab-U6aOiwLfelKzkOWphF3mQy4ShXjMFDYAqykNGR2HqhcuYw9I3vlspQvCBVgc4ELkjMeRV4qAqFSj_mB4kwKJ8qCIRk1v2SSmSr32GxlkdRqi9BLAIKkgWBI3rejL3V1l7-Me9uAksD0izE1UcpltUrAAA5Y6MH3GJLnGqT2Sg26QxL04GsHYGn3_pGymNcl3g3BXt75zENysP3DvSJ766tKvgbzeZ2-qcn6B571zBw |
| linkProvider | Geneva Foundation for Medical Education and Research |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Anti-human+TREM2+induces+microglia+proliferation+and+reduces+pathology+in+an+Alzheimer%E2%80%99s+disease+model&rft.jtitle=The+Journal+of+experimental+medicine&rft.au=Wang%2C+Shoutang&rft.au=Mustafa%2C+Meer&rft.au=Yuede%2C+Carla+M.&rft.au=Salazar%2C+Santiago+Viveros&rft.date=2020-09-07&rft.pub=Rockefeller+University+Press&rft.issn=0022-1007&rft.eissn=1540-9538&rft.volume=217&rft.issue=9&rft_id=info:doi/10.1084%2Fjem.20200785&rft_id=info%3Apmid%2F32579671&rft.externalDocID=PMC7478730 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0022-1007&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0022-1007&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0022-1007&client=summon |