Higher CSF sTREM2 and microglia activation are associated with slower rates of beta-amyloid accumulation

Microglia activation is the brain's major immune response to amyloid plaques in Alzheimer's disease (AD). Both cerebrospinal fluid (CSF) levels of soluble TREM2 (sTREM2), a biomarker of microglia activation, and microglia PET are increased in AD; however, whether an increase in the...

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Detalhes bibliográficos
Autores: Ewers, Michael, Biechele, Gloria, Suárez-Calvet, Marc, Sacher, Christian, Blume, Tanja, Morenas-Rodriguez, Estrella, Deming, Yuetiva, Piccio, Laura, Cruchaga, Carlos, Kleinberger, Gernot, Shaw, Leslie, Trojanowski, John Q., Herms, Jochen, Dichgans, Martin, Alzheimer’s Disease Neuroimaging Initiative, Brendel, Matthias, Haass, Christian, Franzmeier, Nicolai
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2020
País:España
Recursos:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/47940
Acesso em linha:http://hdl.handle.net/10230/47940
http://dx.doi.org/10.15252/emmm.202012308
Access Level:acceso abierto
Palavra-chave:TREM2
Beta-amyloid accumulation
Microglia
Protective
Tau
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spelling Higher CSF sTREM2 and microglia activation are associated with slower rates of beta-amyloid accumulationEwers, MichaelBiechele, GloriaSuárez-Calvet, MarcSacher, ChristianBlume, TanjaMorenas-Rodriguez, EstrellaDeming, YuetivaPiccio, LauraCruchaga, CarlosKleinberger, GernotShaw, LeslieTrojanowski, John Q.Herms, JochenDichgans, MartinAlzheimer’s Disease Neuroimaging InitiativeBrendel, MatthiasHaass, ChristianFranzmeier, NicolaiTREM2Beta-amyloid accumulationMicrogliaProtectiveTauMicroglia activation is the brain's major immune response to amyloid plaques in Alzheimer's disease (AD). Both cerebrospinal fluid (CSF) levels of soluble TREM2 (sTREM2), a biomarker of microglia activation, and microglia PET are increased in AD; however, whether an increase in these biomarkers is associated with reduced amyloid-beta (Aβ) accumulation remains unclear. To address this question, we pursued a two-pronged translational approach. Firstly, in non-demented and demented individuals, we tested CSF sTREM2 at baseline to predict (i) amyloid PET changes over ∼2 years and (ii) tau PET cross-sectionally assessed in a subset of patients. We found higher CSF sTREM2 associated with attenuated amyloid PET increase and lower tau PET. Secondly, in the AppNL-G-F mouse model of amyloidosis, we studied baseline 18 F-GE180 microglia PET and longitudinal amyloid PET to test the microglia vs. Aβ association, without any confounding co-pathologies often present in AD patients. Higher microglia PET at age 5 months was associated with a slower amyloid PET increase between ages 5-to-10 months. In conclusion, higher microglia activation as determined by CSF sTREM2 or microglia PET shows protective effects on subsequent amyloid accumulation.Wiley202120212020info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/47940http://dx.doi.org/10.15252/emmm.202012308reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésCopyright © 2020 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/479402026-06-12T07:21:37Z
dc.title.none.fl_str_mv Higher CSF sTREM2 and microglia activation are associated with slower rates of beta-amyloid accumulation
title Higher CSF sTREM2 and microglia activation are associated with slower rates of beta-amyloid accumulation
spellingShingle Higher CSF sTREM2 and microglia activation are associated with slower rates of beta-amyloid accumulation
Ewers, Michael
TREM2
Beta-amyloid accumulation
Microglia
Protective
Tau
title_short Higher CSF sTREM2 and microglia activation are associated with slower rates of beta-amyloid accumulation
title_full Higher CSF sTREM2 and microglia activation are associated with slower rates of beta-amyloid accumulation
title_fullStr Higher CSF sTREM2 and microglia activation are associated with slower rates of beta-amyloid accumulation
title_full_unstemmed Higher CSF sTREM2 and microglia activation are associated with slower rates of beta-amyloid accumulation
title_sort Higher CSF sTREM2 and microglia activation are associated with slower rates of beta-amyloid accumulation
dc.creator.none.fl_str_mv Ewers, Michael
Biechele, Gloria
Suárez-Calvet, Marc
Sacher, Christian
Blume, Tanja
Morenas-Rodriguez, Estrella
Deming, Yuetiva
Piccio, Laura
Cruchaga, Carlos
Kleinberger, Gernot
Shaw, Leslie
Trojanowski, John Q.
Herms, Jochen
Dichgans, Martin
Alzheimer’s Disease Neuroimaging Initiative
Brendel, Matthias
Haass, Christian
Franzmeier, Nicolai
author Ewers, Michael
author_facet Ewers, Michael
Biechele, Gloria
Suárez-Calvet, Marc
Sacher, Christian
Blume, Tanja
Morenas-Rodriguez, Estrella
Deming, Yuetiva
Piccio, Laura
Cruchaga, Carlos
Kleinberger, Gernot
Shaw, Leslie
Trojanowski, John Q.
Herms, Jochen
Dichgans, Martin
Alzheimer’s Disease Neuroimaging Initiative
Brendel, Matthias
Haass, Christian
Franzmeier, Nicolai
author_role author
author2 Biechele, Gloria
Suárez-Calvet, Marc
Sacher, Christian
Blume, Tanja
Morenas-Rodriguez, Estrella
Deming, Yuetiva
Piccio, Laura
Cruchaga, Carlos
Kleinberger, Gernot
Shaw, Leslie
Trojanowski, John Q.
Herms, Jochen
Dichgans, Martin
Alzheimer’s Disease Neuroimaging Initiative
Brendel, Matthias
Haass, Christian
Franzmeier, Nicolai
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv TREM2
Beta-amyloid accumulation
Microglia
Protective
Tau
topic TREM2
Beta-amyloid accumulation
Microglia
Protective
Tau
description Microglia activation is the brain's major immune response to amyloid plaques in Alzheimer's disease (AD). Both cerebrospinal fluid (CSF) levels of soluble TREM2 (sTREM2), a biomarker of microglia activation, and microglia PET are increased in AD; however, whether an increase in these biomarkers is associated with reduced amyloid-beta (Aβ) accumulation remains unclear. To address this question, we pursued a two-pronged translational approach. Firstly, in non-demented and demented individuals, we tested CSF sTREM2 at baseline to predict (i) amyloid PET changes over ∼2 years and (ii) tau PET cross-sectionally assessed in a subset of patients. We found higher CSF sTREM2 associated with attenuated amyloid PET increase and lower tau PET. Secondly, in the AppNL-G-F mouse model of amyloidosis, we studied baseline 18 F-GE180 microglia PET and longitudinal amyloid PET to test the microglia vs. Aβ association, without any confounding co-pathologies often present in AD patients. Higher microglia PET at age 5 months was associated with a slower amyloid PET increase between ages 5-to-10 months. In conclusion, higher microglia activation as determined by CSF sTREM2 or microglia PET shows protective effects on subsequent amyloid accumulation.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/47940
http://dx.doi.org/10.15252/emmm.202012308
url http://hdl.handle.net/10230/47940
http://dx.doi.org/10.15252/emmm.202012308
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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