{"id":"https://openalex.org/W2998844697","doi":null,"title":"Unraveling How Dysfunction of the Microglial Gene TREM2 Increases Risk for Alzheimer's Disease","display_name":"Unraveling How Dysfunction of the Microglial Gene TREM2 Increases Risk for Alzheimer's Disease","publication_year":2019,"publication_date":"2019-01-01","ids":{"openalex":"https://openalex.org/W2998844697","mag":"2998844697"},"language":"en","primary_location":{"id":"pmh:oai:escholarship.org/ark:/13030/qt40q153wt","doi":null,"is_oa":false,"landing_page_url":"https://escholarship.org/uc/item/40q153wt","pdf_url":null,"source":{"id":"https://openalex.org/S4306400115","display_name":"eScholarship (California Digital Library)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2801248553","host_organization_name":"California Digital Library","host_organization_lineage":["https://openalex.org/I2801248553"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"etd"},"volume":null,"type":"dissertation","is_traditional":true,"indexed_in":[],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5087929308","display_name":"Faten A. Sayed","orcid":"https://orcid.org/0000-0003-3992-4668","observed_orcids":["https://orcid.org/0000-0003-3992-4668"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Faten A. Sayed","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0003-3992-4668","affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5087929308"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11266","display_name":"Neuroinflammation and Neurodegeneration Mechanisms","score":0.9096999764442444,"subfield":{"id":"https://openalex.org/subfields/2808","display_name":"Neurology"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11266","display_name":"Neuroinflammation and Neurodegeneration Mechanisms","score":0.9096999764442444,"subfield":{"id":"https://openalex.org/subfields/2808","display_name":"Neurology"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10086","display_name":"Alzheimer's disease research and treatments","score":0.09000000357627869,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T14144","display_name":"Neurological Disease Mechanisms and Treatments","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2808","display_name":"Neurology"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/trem2","display_name":"TREM2","score":0.9620000123977661},{"id":"https://openalex.org/keywords/alzheimer-s-disease","display_name":"Alzheimer's disease","score":0.9459999799728394},{"id":"https://openalex.org/keywords/microglia","display_name":"microglia","score":0.9120000004768372},{"id":"https://openalex.org/keywords/haploinsufficiency","display_name":"haploinsufficiency","score":0.859000027179718},{"id":"https://openalex.org/keywords/tauopathy","display_name":"tauopathy","score":0.9210000038146973},{"id":"https://openalex.org/keywords/neuroinflammation","display_name":"neuroinflammation","score":0.871999979019165},{"id":"https://openalex.org/keywords/oligodendrocytes","display_name":"oligodendrocytes","score":0.7990000247955322},{"id":"https://openalex.org/keywords/mitochondrial-dysfunction","display_name":"mitochondrial dysfunction","score":0.9359999895095825},{"id":"https://openalex.org/keywords/oxidative-phosphorylation","display_name":"oxidative phosphorylation","score":0.9929999709129333},{"id":"https://openalex.org/keywords/hippocampal-synaptic-transmission","display_name":"hippocampal synaptic transmission","score":0.8410000205039978},{"id":"https://openalex.org/keywords/spatial-memory","display_name":"spatial memory","score":0.9350000023841858},{"id":"https://openalex.org/keywords/neurodegeneration","display_name":"neurodegeneration","score":0.8339999914169312},{"id":"https://openalex.org/keywords/amyloid-plaques","display_name":"amyloid plaques","score":0.75}],"concepts":[{"id":"https://openalex.org/C2779685842","wikidata":"https://www.wikidata.org/wiki/Q18040973","display_name":"TREM2","level":4,"score":0.9905518293380737},{"id":"https://openalex.org/C2779830541","wikidata":"https://www.wikidata.org/wiki/Q1622829","display_name":"Microglia","level":3,"score":0.8472682237625122},{"id":"https://openalex.org/C2776925932","wikidata":"https://www.wikidata.org/wiki/Q1755122","display_name":"Neurodegeneration","level":3,"score":0.6935619115829468},{"id":"https://openalex.org/C2779343474","wikidata":"https://www.wikidata.org/wiki/Q3109175","display_name":"Context (archaeology)","level":2,"score":0.6598789691925049},{"id":"https://openalex.org/C68838962","wikidata":"https://www.wikidata.org/wiki/Q852654","display_name":"Haploinsufficiency","level":4,"score":0.5740494728088379},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.527722954750061},{"id":"https://openalex.org/C164027704","wikidata":"https://www.wikidata.org/wiki/Q3491837","display_name":"Proinflammatory cytokine","level":3,"score":0.4374772906303406},{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.4267209768295288},{"id":"https://openalex.org/C2776914184","wikidata":"https://www.wikidata.org/wiki/Q101991","display_name":"Inflammation","level":2,"score":0.38512396812438965},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.3764321804046631},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.35290446877479553},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.3032594919204712},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.24548453092575073},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.2387222945690155},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.21194183826446533},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.20878607034683228},{"id":"https://openalex.org/C151730666","wikidata":"https://www.wikidata.org/wiki/Q7205","display_name":"Paleontology","level":1,"score":0.0},{"id":"https://openalex.org/C127716648","wikidata":"https://www.wikidata.org/wiki/Q104053","display_name":"Phenotype","level":3,"score":0.0}],"mesh":[],"locations_count":2,"locations":[{"id":"pmh:oai:escholarship.org/ark:/13030/qt40q153wt","doi":null,"is_oa":false,"landing_page_url":"https://escholarship.org/uc/item/40q153wt","pdf_url":null,"source":{"id":"https://openalex.org/S4306400115","display_name":"eScholarship (California Digital Library)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2801248553","host_organization_name":"California Digital Library","host_organization_lineage":["https://openalex.org/I2801248553"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"etd"},{"id":"mag:2998844697","doi":null,"is_oa":false,"landing_page_url":"https://escholarship.org/uc/item/40q153wt","pdf_url":null,"source":null,"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.9763000011444092,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2890556232","https://openalex.org/W3160918637","https://openalex.org/W7171274460","https://openalex.org/W3034536401","https://openalex.org/W2123047934","https://openalex.org/W3214469080","https://openalex.org/W2802366055","https://openalex.org/W2976432777","https://openalex.org/W4408747406","https://openalex.org/W2890072216"],"abstract_inverted_index":{"A":[0],"heterozygous":[1],"single":[2,218,366],"amino":[3,219,367],"acid":[4,220,368],"change":[5,221,369],"in":[6,31,66,90,120,125,146,165,171,182,185,222,282,297,329,344,370,374,384,391,406],"the":[7,20,61,91,97,110,121,126,202,249,268,321,341,375,388,397],"TREM2":[8,223,245],"gene":[9,354],"significantly":[10,138],"increases":[11,224],"risk":[12,225],"for":[13,226],"developing":[14],"late-onset":[15],"Alzheimer\u2019s":[16],"Disease":[17],"(AD).":[18],"In":[19,267,339],"brain,":[21],"Trem2":[22,34,64,88,113,137,159,172,186,198,252],"is":[23,35,100],"uniquely":[24],"expressed":[25],"by":[26,248],"microglia,":[27],"strongly":[28],"implicating":[29],"microglia":[30,293],"AD":[32,318],"pathogenesis.":[33],"a":[36,55,149,217,353,365],"receptor":[37],"with":[38,190,320],"numerous":[39],"ligands":[40],"and":[41,49,79,115,124,196,211,263,276,280,287,299,304,317,336,363],"pleiotropic":[42],"functions":[43],"ranging":[44],"from":[45],"phagocytosis":[46],"to":[47,142,144,148,231,302,333],"inflammation":[48],"synapse":[50],"pruning.":[51],"There":[52],"has":[53],"been":[54],"significant":[56,310,326],"amount":[57],"of":[58,63,82,87,93,112,128,136,156,193,208,240,270,285,352,399],"research":[59],"on":[60,96,117,201],"consequences":[62],"deficiency":[65,89,116],"amyloid":[67],"mouse":[68,235,251,315],"models.":[69],"Trem2-deficient":[70],"mice":[71,161,174,188],"exhibit":[72],"reduced":[73,80,206],"microglial":[74,118,289,404],"clustering":[75],"around":[76],"amyloid-beta":[77],"plaques":[78],"levels":[81,192,207,284],"inflammatory":[83],"transcripts.":[84,290],"The":[85,180,324],"consequence":[86],"context":[92,127,269],"tau":[94,166,169,183],"pathology,":[95],"other":[98,203],"hand,":[99,204],"not":[101],"well":[102],"understood.":[103],"To":[104,214],"address":[105],"this":[106,345,392],"gap,":[107],"we":[108,228],"investigated":[109],"effects":[111],"haploinsufficiency":[114],"function":[119],"healthy":[122],"brain":[123,376],"tauopathy.":[129],"We":[130,254],"found":[131,255],"that":[132,256],"removing":[133,153],"one":[134,238,350,371],"copy":[135,239,351],"impaired":[139,264],"microglia\u2019s":[140],"ability":[141],"respond":[143],"injury":[145],"vivo":[147],"greater":[150],"extent":[151],"than":[152,359],"both":[154,361],"copies":[155,362],"Trem2.":[157],"Moreover,":[158,291],"haploinsufficient":[160,187],"exhibited":[162,205],"an":[163],"increase":[164,181],"load,":[167],"whereas":[168],"load":[170,184],"deficient":[173,199],"was":[175,309,328],"unimpacted":[176],"or":[177,242],"slightly":[178],"reduced.":[179],"correlated":[189],"increased":[191],"pro-inflammatory":[194,209,286],"transcripts":[195,210,331],"neurodegeneration.":[197,213],"mice,":[200],"less":[212],"determine":[215],"how":[216,348,364],"AD,":[227],"used":[229],"CRISPR":[230],"generate":[232],"two":[233],"novel":[234],"models":[236],"expressing":[237],"wild-type":[241],"R47H":[243,322],"human":[244],"(R47H-hTREM2)":[246],"driven":[247],"endogenous":[250],"promoter.":[253],"R47H-hTREM2":[257,292,314],"caused":[258,294],"aberrant":[259],"hippocampal":[260],"synaptic":[261],"transmission":[262],"spatial":[265,274],"memory.":[266],"tauopathy,":[271],"it":[272],"exacerbated":[273],"learning":[275],"memory":[277],"as":[278],"well,":[279],"resulted":[281],"higher":[283],"disease-associated":[288],"transcriptional":[295],"changes":[296],"neurons":[298],"oligodendrocytes,":[300],"pertaining":[301],"metabolism":[303],"oxidative":[305,337],"phosphorylation.":[306,338],"Lastly,":[307],"there":[308],"overlap":[311,327],"between":[312],"our":[313],"model":[316],"patients":[319],"mutation.":[323],"most":[325],"oligodendrocyte":[330],"related":[332],"mitochondrial":[334],"dysfunction":[335,405],"sum,":[340],"work":[342,393],"highlighted":[343,390],"dissertation":[346],"highlights":[347],"losing":[349,360],"can":[355,377,394],"be":[356],"more":[357],"detrimental":[358],"cell":[372],"type":[373],"have":[378],"widespread":[379],"non-cell":[380],"autonomous":[381],"ramifications":[382],"resulting":[383],"cognitive":[385],"deficits.":[386],"Hopefully,":[387],"pathways":[389],"help":[395],"guide":[396],"development":[398],"therapeutic":[400],"strategies":[401],"targeted":[402],"at":[403],"AD.":[407]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2020-01-23T00:00:00"}