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000140448 0247_ $$2doi$$a10.1038/s41593-018-0296-9
000140448 0247_ $$2pmid$$apmid:30617257
000140448 0247_ $$2pmc$$apmc:PMC6417433
000140448 0247_ $$2ISSN$$a1097-6256
000140448 0247_ $$2ISSN$$a1471-003X
000140448 0247_ $$2ISSN$$a1471-0048
000140448 0247_ $$2ISSN$$a1546-1726
000140448 0247_ $$2altmetric$$aaltmetric:53589064
000140448 037__ $$aDZNE-2020-06770
000140448 041__ $$aEnglish
000140448 082__ $$a570
000140448 1001_ $$aParhizkar, Samira$$b0
000140448 245__ $$aLoss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE.
000140448 260__ $$aLondon$$bNature Publ. Group58142$$c2019
000140448 264_1 $$2Crossref$$3online$$bSpringer Science and Business Media LLC$$c2019-01-07
000140448 264_1 $$2Crossref$$3print$$bSpringer Science and Business Media LLC$$c2019-02-01
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000140448 520__ $$aCoding variants in the triggering receptor expressed on myeloid cells 2 (TREM2) are associated with late-onset Alzheimer's disease (AD). We demonstrate that amyloid plaque seeding is increased in the absence of functional Trem2. Increased seeding is accompanied by decreased microglial clustering around newly seeded plaques and reduced plaque-associated apolipoprotein E (ApoE). Reduced ApoE deposition in plaques is also observed in brains of AD patients carrying TREM2 coding variants. Proteomic analyses and microglia depletion experiments revealed microglia as one origin of plaque-associated ApoE. Longitudinal amyloid small animal positron emission tomography demonstrates accelerated amyloidogenesis in Trem2 loss-of-function mutants at early stages, which progressed at a lower rate with aging. These findings suggest that in the absence of functional Trem2, early amyloidogenesis is accelerated due to reduced phagocytic clearance of amyloid seeds despite reduced plaque-associated ApoE.
000140448 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0
000140448 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x1
000140448 542__ $$2Crossref$$i2019-01-07$$uhttp://www.springer.com/tdm
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000140448 650_7 $$2NLM Chemicals$$aAmyloid
000140448 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000140448 650_7 $$2NLM Chemicals$$aAmyloid beta-Protein Precursor
000140448 650_7 $$2NLM Chemicals$$aApolipoproteins E
000140448 650_7 $$2NLM Chemicals$$aMembrane Glycoproteins
000140448 650_7 $$2NLM Chemicals$$aReceptors, Immunologic
000140448 650_7 $$2NLM Chemicals$$aTrem2 protein, mouse
000140448 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000140448 650_2 $$2MeSH$$aAlzheimer Disease: metabolism
000140448 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000140448 650_2 $$2MeSH$$aAmyloid: metabolism
000140448 650_2 $$2MeSH$$aAmyloid beta-Peptides: genetics
000140448 650_2 $$2MeSH$$aAmyloid beta-Peptides: metabolism
000140448 650_2 $$2MeSH$$aAmyloid beta-Protein Precursor: genetics
000140448 650_2 $$2MeSH$$aAmyloid beta-Protein Precursor: metabolism
000140448 650_2 $$2MeSH$$aAnimals
000140448 650_2 $$2MeSH$$aApolipoproteins E: metabolism
000140448 650_2 $$2MeSH$$aBrain: metabolism
000140448 650_2 $$2MeSH$$aBrain: pathology
000140448 650_2 $$2MeSH$$aDisease Models, Animal
000140448 650_2 $$2MeSH$$aGenotype
000140448 650_2 $$2MeSH$$aHumans
000140448 650_2 $$2MeSH$$aMembrane Glycoproteins: genetics
000140448 650_2 $$2MeSH$$aMembrane Glycoproteins: metabolism
000140448 650_2 $$2MeSH$$aMice
000140448 650_2 $$2MeSH$$aMice, Transgenic
000140448 650_2 $$2MeSH$$aMicroglia: metabolism
000140448 650_2 $$2MeSH$$aMicroglia: pathology
000140448 650_2 $$2MeSH$$aPhagocytosis: physiology
000140448 650_2 $$2MeSH$$aPlaque, Amyloid: genetics
000140448 650_2 $$2MeSH$$aPlaque, Amyloid: metabolism
000140448 650_2 $$2MeSH$$aPlaque, Amyloid: pathology
000140448 650_2 $$2MeSH$$aReceptors, Immunologic: genetics
000140448 650_2 $$2MeSH$$aReceptors, Immunologic: metabolism
000140448 7001_ $$0P:(DE-2719)2811333$$aArzberger, Thomas$$b1
000140448 7001_ $$0P:(DE-2719)9001539$$aBrendel, Matthias$$b2$$udzne
000140448 7001_ $$0P:(DE-HGF)0$$aKleinberger, Gernot$$b3
000140448 7001_ $$aDeussing, Maximilian$$b4
000140448 7001_ $$aFocke, Carola$$b5
000140448 7001_ $$0P:(DE-HGF)0$$aNuscher, Brigitte$$b6
000140448 7001_ $$aXiong, Monica$$b7
000140448 7001_ $$aGhasemigharagoz, Alireza$$b8
000140448 7001_ $$aKatzmarski, Natalie$$b9
000140448 7001_ $$aKrasemann, Susanne$$b10
000140448 7001_ $$0P:(DE-2719)2181459$$aLichtenthaler, Stefan F$$b11
000140448 7001_ $$0P:(DE-2719)2810938$$aMüller, Stephan A$$b12
000140448 7001_ $$0P:(DE-2719)2340744$$aColombo, Alessio$$b13
000140448 7001_ $$0P:(DE-2719)2812269$$aSebastian Monasor, Laura$$b14
000140448 7001_ $$0P:(DE-2719)2442036$$aTahirovic, Sabina$$b15
000140448 7001_ $$0P:(DE-2719)2810441$$aHerms, Jochen$$b16
000140448 7001_ $$0P:(DE-HGF)0$$aWillem, Michael$$b17
000140448 7001_ $$aPettkus, Nadine$$b18
000140448 7001_ $$aButovsky, Oleg$$b19
000140448 7001_ $$aBartenstein, Peter$$b20
000140448 7001_ $$0P:(DE-2719)2231621$$aEdbauer, Dieter$$b21
000140448 7001_ $$0P:(DE-HGF)0$$aRominger, Axel$$b22
000140448 7001_ $$aErtürk, Ali$$b23
000140448 7001_ $$0P:(DE-HGF)0$$aGrathwohl, Stefan A$$b24
000140448 7001_ $$0P:(DE-2719)2811021$$aNeher, Jonas J$$b25
000140448 7001_ $$aHoltzman, David M$$b26
000140448 7001_ $$0P:(DE-HGF)0$$aMeyer-Luehmann, Melanie$$b27
000140448 7001_ $$0P:(DE-2719)2202037$$aHaass, Christian$$b28$$eLast author
000140448 77318 $$2Crossref$$3journal-article$$a10.1038/s41593-018-0296-9$$b : Springer Science and Business Media LLC, 2019-01-07$$n2$$p191-204$$tNature Neuroscience$$v22$$x1097-6256$$y2019
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000140448 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417433
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