001     140448
005     20241206141012.0
024 7 _ |a 10.1038/s41593-018-0296-9
|2 doi
024 7 _ |a pmid:30617257
|2 pmid
024 7 _ |a pmc:PMC6417433
|2 pmc
024 7 _ |a 1097-6256
|2 ISSN
024 7 _ |a 1471-003X
|2 ISSN
024 7 _ |a 1471-0048
|2 ISSN
024 7 _ |a 1546-1726
|2 ISSN
024 7 _ |a altmetric:53589064
|2 altmetric
037 _ _ |a DZNE-2020-06770
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Parhizkar, Samira
|b 0
245 _ _ |a Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE.
260 _ _ |a London
|c 2019
|b Nature Publ. Group58142
264 _ 1 |3 online
|2 Crossref
|b Springer Science and Business Media LLC
|c 2019-01-07
264 _ 1 |3 print
|2 Crossref
|b Springer Science and Business Media LLC
|c 2019-02-01
336 7 _ |a article
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a Coding 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.
536 _ _ |a 342 - Disease Mechanisms and Model Systems (POF3-342)
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542 _ _ |i 2019-01-07
|2 Crossref
|u http://www.springer.com/tdm
588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 7 |a Amyloid
|2 NLM Chemicals
650 _ 7 |a Amyloid beta-Peptides
|2 NLM Chemicals
650 _ 7 |a Amyloid beta-Protein Precursor
|2 NLM Chemicals
650 _ 7 |a Apolipoproteins E
|2 NLM Chemicals
650 _ 7 |a Membrane Glycoproteins
|2 NLM Chemicals
650 _ 7 |a Receptors, Immunologic
|2 NLM Chemicals
650 _ 7 |a Trem2 protein, mouse
|2 NLM Chemicals
650 _ 2 |a Alzheimer Disease: genetics
|2 MeSH
650 _ 2 |a Alzheimer Disease: metabolism
|2 MeSH
650 _ 2 |a Alzheimer Disease: pathology
|2 MeSH
650 _ 2 |a Amyloid: metabolism
|2 MeSH
650 _ 2 |a Amyloid beta-Peptides: genetics
|2 MeSH
650 _ 2 |a Amyloid beta-Peptides: metabolism
|2 MeSH
650 _ 2 |a Amyloid beta-Protein Precursor: genetics
|2 MeSH
650 _ 2 |a Amyloid beta-Protein Precursor: metabolism
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Apolipoproteins E: metabolism
|2 MeSH
650 _ 2 |a Brain: metabolism
|2 MeSH
650 _ 2 |a Brain: pathology
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Genotype
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Membrane Glycoproteins: genetics
|2 MeSH
650 _ 2 |a Membrane Glycoproteins: metabolism
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Mice, Transgenic
|2 MeSH
650 _ 2 |a Microglia: metabolism
|2 MeSH
650 _ 2 |a Microglia: pathology
|2 MeSH
650 _ 2 |a Phagocytosis: physiology
|2 MeSH
650 _ 2 |a Plaque, Amyloid: genetics
|2 MeSH
650 _ 2 |a Plaque, Amyloid: metabolism
|2 MeSH
650 _ 2 |a Plaque, Amyloid: pathology
|2 MeSH
650 _ 2 |a Receptors, Immunologic: genetics
|2 MeSH
650 _ 2 |a Receptors, Immunologic: metabolism
|2 MeSH
700 1 _ |a Arzberger, Thomas
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700 1 _ |a Kleinberger, Gernot
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700 1 _ |a Deussing, Maximilian
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700 1 _ |a Focke, Carola
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700 1 _ |a Nuscher, Brigitte
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700 1 _ |a Xiong, Monica
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700 1 _ |a Ghasemigharagoz, Alireza
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700 1 _ |a Katzmarski, Natalie
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700 1 _ |a Krasemann, Susanne
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700 1 _ |a Lichtenthaler, Stefan F
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700 1 _ |a Müller, Stephan A
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700 1 _ |a Colombo, Alessio
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700 1 _ |a Sebastian Monasor, Laura
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700 1 _ |a Tahirovic, Sabina
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700 1 _ |a Herms, Jochen
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700 1 _ |a Willem, Michael
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700 1 _ |a Pettkus, Nadine
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700 1 _ |a Butovsky, Oleg
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700 1 _ |a Bartenstein, Peter
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700 1 _ |a Edbauer, Dieter
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700 1 _ |a Rominger, Axel
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700 1 _ |a Ertürk, Ali
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700 1 _ |a Grathwohl, Stefan A
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700 1 _ |a Neher, Jonas J
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700 1 _ |a Holtzman, David M
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700 1 _ |a Meyer-Luehmann, Melanie
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700 1 _ |a Haass, Christian
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773 1 8 |a 10.1038/s41593-018-0296-9
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|v 22
|y 2019
|x 1097-6256
773 _ _ |a 10.1038/s41593-018-0296-9
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856 7 _ |2 Pubmed Central
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LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21