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Increase of TREM2 during Aging of an Alzheimer’s Disease Mouse Model Is Paralleled by Microglial Activation and Amyloidosis

Heterozygous missense mutations in the triggering receptor expressed on myeloid cells 2 (TREM2) have been reported to significantly increase the risk of developing Alzheimer’s disease (AD). Since TREM2 is specifically expressed by microglia in the brain, we hypothesized that soluble TREM2 (sTREM2) l...

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Autores principales: Brendel, Matthias, Kleinberger, Gernot, Probst, Federico, Jaworska, Anna, Overhoff, Felix, Blume, Tanja, Albert, Nathalie L., Carlsen, Janette, Lindner, Simon, Gildehaus, Franz Josef, Ozmen, Laurence, Suárez-Calvet, Marc, Bartenstein, Peter, Baumann, Karlheinz, Ewers, Michael, Herms, Jochen, Haass, Christian, Rominger, Axel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5282474/
https://www.ncbi.nlm.nih.gov/pubmed/28197095
http://dx.doi.org/10.3389/fnagi.2017.00008
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author Brendel, Matthias
Kleinberger, Gernot
Probst, Federico
Jaworska, Anna
Overhoff, Felix
Blume, Tanja
Albert, Nathalie L.
Carlsen, Janette
Lindner, Simon
Gildehaus, Franz Josef
Ozmen, Laurence
Suárez-Calvet, Marc
Bartenstein, Peter
Baumann, Karlheinz
Ewers, Michael
Herms, Jochen
Haass, Christian
Rominger, Axel
author_facet Brendel, Matthias
Kleinberger, Gernot
Probst, Federico
Jaworska, Anna
Overhoff, Felix
Blume, Tanja
Albert, Nathalie L.
Carlsen, Janette
Lindner, Simon
Gildehaus, Franz Josef
Ozmen, Laurence
Suárez-Calvet, Marc
Bartenstein, Peter
Baumann, Karlheinz
Ewers, Michael
Herms, Jochen
Haass, Christian
Rominger, Axel
author_sort Brendel, Matthias
collection PubMed
description Heterozygous missense mutations in the triggering receptor expressed on myeloid cells 2 (TREM2) have been reported to significantly increase the risk of developing Alzheimer’s disease (AD). Since TREM2 is specifically expressed by microglia in the brain, we hypothesized that soluble TREM2 (sTREM2) levels may increase together with in vivo biomarkers of microglial activity and amyloidosis in an AD mouse model as assessed by small animal positron-emission-tomography (μPET). In this cross-sectional study, we examined a strong amyloid mouse model (PS2APP) of four age groups by μPET with [(18)F]-GE180 (glial activation) and [(18)F]-florbetaben (amyloidosis), followed by measurement of sTREM2 levels and amyloid levels in the brain. Pathology affected brain regions were compared between tracers (dice similarity coefficients) and pseudo-longitudinally. μPET results of both tracers were correlated with terminal TREM2 levels. The brain sTREM2 levels strongly increased with age of PS2APP mice (5 vs. 16 months: +211%, p < 0.001), and correlated highly with μPET signals of microglial activity (R = 0.89, p < 0.001) and amyloidosis (R = 0.92, p < 0.001). Dual μPET enabled regional mapping of glial activation and amyloidosis in the mouse brain, which progressed concertedly leading to a high overlap in aged PS2APP mice (dice similarity 67%). Together, these results substantiate the use of in vivo μPET measurements in conjunction with post mortem sTREM2 in future anti-inflammatory treatment trials. Taking human data into account sTREM2 may increase during active amyloid deposition.
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spelling pubmed-52824742017-02-14 Increase of TREM2 during Aging of an Alzheimer’s Disease Mouse Model Is Paralleled by Microglial Activation and Amyloidosis Brendel, Matthias Kleinberger, Gernot Probst, Federico Jaworska, Anna Overhoff, Felix Blume, Tanja Albert, Nathalie L. Carlsen, Janette Lindner, Simon Gildehaus, Franz Josef Ozmen, Laurence Suárez-Calvet, Marc Bartenstein, Peter Baumann, Karlheinz Ewers, Michael Herms, Jochen Haass, Christian Rominger, Axel Front Aging Neurosci Neuroscience Heterozygous missense mutations in the triggering receptor expressed on myeloid cells 2 (TREM2) have been reported to significantly increase the risk of developing Alzheimer’s disease (AD). Since TREM2 is specifically expressed by microglia in the brain, we hypothesized that soluble TREM2 (sTREM2) levels may increase together with in vivo biomarkers of microglial activity and amyloidosis in an AD mouse model as assessed by small animal positron-emission-tomography (μPET). In this cross-sectional study, we examined a strong amyloid mouse model (PS2APP) of four age groups by μPET with [(18)F]-GE180 (glial activation) and [(18)F]-florbetaben (amyloidosis), followed by measurement of sTREM2 levels and amyloid levels in the brain. Pathology affected brain regions were compared between tracers (dice similarity coefficients) and pseudo-longitudinally. μPET results of both tracers were correlated with terminal TREM2 levels. The brain sTREM2 levels strongly increased with age of PS2APP mice (5 vs. 16 months: +211%, p < 0.001), and correlated highly with μPET signals of microglial activity (R = 0.89, p < 0.001) and amyloidosis (R = 0.92, p < 0.001). Dual μPET enabled regional mapping of glial activation and amyloidosis in the mouse brain, which progressed concertedly leading to a high overlap in aged PS2APP mice (dice similarity 67%). Together, these results substantiate the use of in vivo μPET measurements in conjunction with post mortem sTREM2 in future anti-inflammatory treatment trials. Taking human data into account sTREM2 may increase during active amyloid deposition. Frontiers Media S.A. 2017-01-31 /pmc/articles/PMC5282474/ /pubmed/28197095 http://dx.doi.org/10.3389/fnagi.2017.00008 Text en Copyright © 2017 Brendel, Kleinberger, Probst, Jaworska, Overhoff, Blume, Albert, Carlsen, Lindner, Gildehaus, Ozmen, Suárez-Calvet, Bartenstein, Baumann, Ewers, Herms, Haass and Rominger. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Brendel, Matthias
Kleinberger, Gernot
Probst, Federico
Jaworska, Anna
Overhoff, Felix
Blume, Tanja
Albert, Nathalie L.
Carlsen, Janette
Lindner, Simon
Gildehaus, Franz Josef
Ozmen, Laurence
Suárez-Calvet, Marc
Bartenstein, Peter
Baumann, Karlheinz
Ewers, Michael
Herms, Jochen
Haass, Christian
Rominger, Axel
Increase of TREM2 during Aging of an Alzheimer’s Disease Mouse Model Is Paralleled by Microglial Activation and Amyloidosis
title Increase of TREM2 during Aging of an Alzheimer’s Disease Mouse Model Is Paralleled by Microglial Activation and Amyloidosis
title_full Increase of TREM2 during Aging of an Alzheimer’s Disease Mouse Model Is Paralleled by Microglial Activation and Amyloidosis
title_fullStr Increase of TREM2 during Aging of an Alzheimer’s Disease Mouse Model Is Paralleled by Microglial Activation and Amyloidosis
title_full_unstemmed Increase of TREM2 during Aging of an Alzheimer’s Disease Mouse Model Is Paralleled by Microglial Activation and Amyloidosis
title_short Increase of TREM2 during Aging of an Alzheimer’s Disease Mouse Model Is Paralleled by Microglial Activation and Amyloidosis
title_sort increase of trem2 during aging of an alzheimer’s disease mouse model is paralleled by microglial activation and amyloidosis
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5282474/
https://www.ncbi.nlm.nih.gov/pubmed/28197095
http://dx.doi.org/10.3389/fnagi.2017.00008
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