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Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE

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Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE. / Parhizkar, Samira; Arzberger, Thomas; Brendel, Matthias; Kleinberger, Gernot; Deussing, Maximilian; Focke, Carola; Nuscher, Brigitte; Xiong, Monica; Ghasemigharagoz, Alireza; Katzmarski, Natalie; Krasemann, Susanne; Lichtenthaler, Stefan F; Müller, Stephan A; Colombo, Alessio; Monasor, Laura Sebastian; Tahirovic, Sabina; Herms, Jochen; Willem, Michael; Pettkus, Nadine; Butovsky, Oleg; Bartenstein, Peter; Edbauer, Dieter; Rominger, Axel; Ertürk, Ali; Grathwohl, Stefan A; Neher, Jonas J; Holtzman, David M; Meyer-Luehmann, Melanie; Haass, Christian.

In: NAT NEUROSCI, Vol. 22, No. 2, 02.2019, p. 191-204.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Parhizkar, S, Arzberger, T, Brendel, M, Kleinberger, G, Deussing, M, Focke, C, Nuscher, B, Xiong, M, Ghasemigharagoz, A, Katzmarski, N, Krasemann, S, Lichtenthaler, SF, Müller, SA, Colombo, A, Monasor, LS, Tahirovic, S, Herms, J, Willem, M, Pettkus, N, Butovsky, O, Bartenstein, P, Edbauer, D, Rominger, A, Ertürk, A, Grathwohl, SA, Neher, JJ, Holtzman, DM, Meyer-Luehmann, M & Haass, C 2019, 'Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE', NAT NEUROSCI, vol. 22, no. 2, pp. 191-204. https://doi.org/10.1038/s41593-018-0296-9

APA

Parhizkar, S., Arzberger, T., Brendel, M., Kleinberger, G., Deussing, M., Focke, C., Nuscher, B., Xiong, M., Ghasemigharagoz, A., Katzmarski, N., Krasemann, S., Lichtenthaler, S. F., Müller, S. A., Colombo, A., Monasor, L. S., Tahirovic, S., Herms, J., Willem, M., Pettkus, N., ... Haass, C. (2019). Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE. NAT NEUROSCI, 22(2), 191-204. https://doi.org/10.1038/s41593-018-0296-9

Vancouver

Parhizkar S, Arzberger T, Brendel M, Kleinberger G, Deussing M, Focke C et al. Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE. NAT NEUROSCI. 2019 Feb;22(2):191-204. https://doi.org/10.1038/s41593-018-0296-9

Bibtex

@article{ce2653e103fc4f099d2c6fe8eac14779,
title = "Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE",
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.",
keywords = "Alzheimer Disease/genetics, Amyloid/metabolism, Amyloid beta-Peptides/genetics, Amyloid beta-Protein Precursor/genetics, Animals, Apolipoproteins E/metabolism, Brain/metabolism, Disease Models, Animal, Genotype, Humans, Membrane Glycoproteins/genetics, Mice, Mice, Transgenic, Microglia/metabolism, Phagocytosis/physiology, Plaque, Amyloid/genetics, Receptors, Immunologic/genetics",
author = "Samira Parhizkar and Thomas Arzberger and Matthias Brendel and Gernot Kleinberger and Maximilian Deussing and Carola Focke and Brigitte Nuscher and Monica Xiong and Alireza Ghasemigharagoz and Natalie Katzmarski and Susanne Krasemann and Lichtenthaler, {Stefan F} and M{\"u}ller, {Stephan A} and Alessio Colombo and Monasor, {Laura Sebastian} and Sabina Tahirovic and Jochen Herms and Michael Willem and Nadine Pettkus and Oleg Butovsky and Peter Bartenstein and Dieter Edbauer and Axel Rominger and Ali Ert{\"u}rk and Grathwohl, {Stefan A} and Neher, {Jonas J} and Holtzman, {David M} and Melanie Meyer-Luehmann and Christian Haass",
year = "2019",
month = feb,
doi = "10.1038/s41593-018-0296-9",
language = "English",
volume = "22",
pages = "191--204",
journal = "NAT NEUROSCI",
issn = "1097-6256",
publisher = "NATURE PUBLISHING GROUP",
number = "2",

}

RIS

TY - JOUR

T1 - Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE

AU - Parhizkar, Samira

AU - Arzberger, Thomas

AU - Brendel, Matthias

AU - Kleinberger, Gernot

AU - Deussing, Maximilian

AU - Focke, Carola

AU - Nuscher, Brigitte

AU - Xiong, Monica

AU - Ghasemigharagoz, Alireza

AU - Katzmarski, Natalie

AU - Krasemann, Susanne

AU - Lichtenthaler, Stefan F

AU - Müller, Stephan A

AU - Colombo, Alessio

AU - Monasor, Laura Sebastian

AU - Tahirovic, Sabina

AU - Herms, Jochen

AU - Willem, Michael

AU - Pettkus, Nadine

AU - Butovsky, Oleg

AU - Bartenstein, Peter

AU - Edbauer, Dieter

AU - Rominger, Axel

AU - Ertürk, Ali

AU - Grathwohl, Stefan A

AU - Neher, Jonas J

AU - Holtzman, David M

AU - Meyer-Luehmann, Melanie

AU - Haass, Christian

PY - 2019/2

Y1 - 2019/2

N2 - 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.

AB - 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.

KW - Alzheimer Disease/genetics

KW - Amyloid/metabolism

KW - Amyloid beta-Peptides/genetics

KW - Amyloid beta-Protein Precursor/genetics

KW - Animals

KW - Apolipoproteins E/metabolism

KW - Brain/metabolism

KW - Disease Models, Animal

KW - Genotype

KW - Humans

KW - Membrane Glycoproteins/genetics

KW - Mice

KW - Mice, Transgenic

KW - Microglia/metabolism

KW - Phagocytosis/physiology

KW - Plaque, Amyloid/genetics

KW - Receptors, Immunologic/genetics

U2 - 10.1038/s41593-018-0296-9

DO - 10.1038/s41593-018-0296-9

M3 - SCORING: Journal article

C2 - 30617257

VL - 22

SP - 191

EP - 204

JO - NAT NEUROSCI

JF - NAT NEUROSCI

SN - 1097-6256

IS - 2

ER -