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TREM2-Deficient Microglia Attenuate Tau Spreading In Vivo

The role of TREM2 in Alzheimer’s disease (AD) is not fully understood. Previous studies investigating the effect of TREM2 deletion on tauopathy mouse models without the contribution of b-amyloid have focused only on tau overexpression models. Herein, we investigated the effects of TREM2 deficiency o...

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Autores principales: Lee-Gosselin, Audrey, Jury-Garfe, Nur, You, Yanwen, Dabin, Luke, Soni, Disha, Dutta, Sayan, Rochet, Jean-Christophe, Kim, Jungsu, Oblak, Adrian L., Lasagna-Reeves, Cristian A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10296847/
https://www.ncbi.nlm.nih.gov/pubmed/37371067
http://dx.doi.org/10.3390/cells12121597
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author Lee-Gosselin, Audrey
Jury-Garfe, Nur
You, Yanwen
Dabin, Luke
Soni, Disha
Dutta, Sayan
Rochet, Jean-Christophe
Kim, Jungsu
Oblak, Adrian L.
Lasagna-Reeves, Cristian A.
author_facet Lee-Gosselin, Audrey
Jury-Garfe, Nur
You, Yanwen
Dabin, Luke
Soni, Disha
Dutta, Sayan
Rochet, Jean-Christophe
Kim, Jungsu
Oblak, Adrian L.
Lasagna-Reeves, Cristian A.
author_sort Lee-Gosselin, Audrey
collection PubMed
description The role of TREM2 in Alzheimer’s disease (AD) is not fully understood. Previous studies investigating the effect of TREM2 deletion on tauopathy mouse models without the contribution of b-amyloid have focused only on tau overexpression models. Herein, we investigated the effects of TREM2 deficiency on tau spreading using a mouse model in which endogenous tau is seeded to produce AD-like tau features. We found that Trem2(−/−) mice exhibit attenuated tau pathology in multiple brain regions concomitant with a decreased microglial density. The neuroinflammatory profile in TREM2-deficient mice did not induce an activated inflammatory response to tau pathology. These findings suggest that reduced TREM2 signaling may alter the response of microglia to pathological tau aggregates, impairing their activation and decreasing their capacity to contribute to tau spreading. However, caution should be exercised when targeting TREM2 as a therapeutic entry point for AD until its involvement in tau aggregation and propagation is better understood.
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spelling pubmed-102968472023-06-28 TREM2-Deficient Microglia Attenuate Tau Spreading In Vivo Lee-Gosselin, Audrey Jury-Garfe, Nur You, Yanwen Dabin, Luke Soni, Disha Dutta, Sayan Rochet, Jean-Christophe Kim, Jungsu Oblak, Adrian L. Lasagna-Reeves, Cristian A. Cells Article The role of TREM2 in Alzheimer’s disease (AD) is not fully understood. Previous studies investigating the effect of TREM2 deletion on tauopathy mouse models without the contribution of b-amyloid have focused only on tau overexpression models. Herein, we investigated the effects of TREM2 deficiency on tau spreading using a mouse model in which endogenous tau is seeded to produce AD-like tau features. We found that Trem2(−/−) mice exhibit attenuated tau pathology in multiple brain regions concomitant with a decreased microglial density. The neuroinflammatory profile in TREM2-deficient mice did not induce an activated inflammatory response to tau pathology. These findings suggest that reduced TREM2 signaling may alter the response of microglia to pathological tau aggregates, impairing their activation and decreasing their capacity to contribute to tau spreading. However, caution should be exercised when targeting TREM2 as a therapeutic entry point for AD until its involvement in tau aggregation and propagation is better understood. MDPI 2023-06-10 /pmc/articles/PMC10296847/ /pubmed/37371067 http://dx.doi.org/10.3390/cells12121597 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee-Gosselin, Audrey
Jury-Garfe, Nur
You, Yanwen
Dabin, Luke
Soni, Disha
Dutta, Sayan
Rochet, Jean-Christophe
Kim, Jungsu
Oblak, Adrian L.
Lasagna-Reeves, Cristian A.
TREM2-Deficient Microglia Attenuate Tau Spreading In Vivo
title TREM2-Deficient Microglia Attenuate Tau Spreading In Vivo
title_full TREM2-Deficient Microglia Attenuate Tau Spreading In Vivo
title_fullStr TREM2-Deficient Microglia Attenuate Tau Spreading In Vivo
title_full_unstemmed TREM2-Deficient Microglia Attenuate Tau Spreading In Vivo
title_short TREM2-Deficient Microglia Attenuate Tau Spreading In Vivo
title_sort trem2-deficient microglia attenuate tau spreading in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10296847/
https://www.ncbi.nlm.nih.gov/pubmed/37371067
http://dx.doi.org/10.3390/cells12121597
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