Journal Article

DZNE-2020-06770

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE.

Parhizkar, S. ; Arzberger, T.DZNE* ; Brendel, M.Extern* ; Kleinberger, G. ; Deussing, M. ; Focke, C. ; Nuscher, B. ; Xiong, M. ; Ghasemigharagoz, A. ; Katzmarski, N. ; Krasemann, S. ; Lichtenthaler, S. F.DZNE* ; Müller, S. A.DZNE* ; Colombo, A.DZNE* ; Sebastian Monasor, L.DZNE* ; Tahirovic, S.DZNE* ; Herms, J.DZNE* ; Willem, M. ; Pettkus, N. ; Butovsky, O. ; Bartenstein, P. ; Edbauer, D.DZNE* ; Rominger, A. ; Ertürk, A. ; Grathwohl, S. A. ; Neher, J. J.DZNE* ; Holtzman, D. M. ; Meyer-Luehmann, M. ; Haass, C. (Last author)DZNE*

2019
Nature Publ. Group58142 London

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Please use a persistent id in citations: doi:10.1038/s41593-018-0296-9

Abstract: 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.

Keyword(s): Alzheimer Disease: genetics (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Amyloid: metabolism (MeSH) ; Amyloid beta-Peptides: genetics (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Amyloid beta-Protein Precursor: genetics (MeSH) ; Amyloid beta-Protein Precursor: metabolism (MeSH) ; Animals (MeSH) ; Apolipoproteins E: metabolism (MeSH) ; Brain: metabolism (MeSH) ; Brain: pathology (MeSH) ; Disease Models, Animal (MeSH) ; Genotype (MeSH) ; Humans (MeSH) ; Membrane Glycoproteins: genetics (MeSH) ; Membrane Glycoproteins: metabolism (MeSH) ; Mice (MeSH) ; Mice, Transgenic (MeSH) ; Microglia: metabolism (MeSH) ; Microglia: pathology (MeSH) ; Phagocytosis: physiology (MeSH) ; Plaque, Amyloid: genetics (MeSH) ; Plaque, Amyloid: metabolism (MeSH) ; Plaque, Amyloid: pathology (MeSH) ; Receptors, Immunologic: genetics (MeSH) ; Receptors, Immunologic: metabolism (MeSH) ; Amyloid ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; Apolipoproteins E ; Membrane Glycoproteins ; Receptors, Immunologic ; Trem2 protein, mouse

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Contributing Institute(s):

1. Clinical Neurodegeneration (AG Levin)
2. Neuroproteomics (AG Lichtenthaler)
3. Juvenile Neurodegeneration (AG Tahirovic)
4. Translational Brain Research (AG Herms)
5. Molecular Neurodegeneration (AG Haass)
6. Neuroimmunology and Neurodegenerative Disease (AG Neher (Tübingen))
7. Cell Biology of Neurodegeneration (AG Edbauer)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)
2. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2019

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Database coverage:
; BIOSIS Previews ; BIOSIS Reviews Reports And Meetings ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 30 ; JCR ; Nationallizenz ; SCOPUS ; Web of Science Core Collection

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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Journal Article (Erratum/Correction) Parhizkar, S. ; Arzberger, T.DZNE* ; Brendel, M.Extern* ; Kleinberger, G. ; Deussing, M. ; Focke, C. ; Nuscher, B. ; Xiong, M. ; Ghasemigharagoz, A. ; Katzmarski, N. ; Krasemann, S. ; Lichtenthaler, S. F.DZNE* ; Müller, S. A.DZNE* ; Colombo, A. ; Sebastian Monasor, L.DZNE* ; Tahirovic, S.DZNE* ; Herms, J.DZNE* ; Willem, M. ; Pettkus, N. ; Butovsky, O. ; Bartenstein, P. ; Edbauer, D.DZNE* ; Rominger, A. ; Ertürk, A. ; Grathwohl, S. A. ; Neher, J. J.DZNE* ; Holtzman, D. M. ; Meyer-Luehmann, M. ; Haass, C. (Last author)DZNE*
Author Correction: Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE
Nature neuroscience 27(9), 1858 - 1859 (2024) [10.1038/s41593-024-01752-x]2024   Files BibTeX | EndNote: XML, Text | RIS

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