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Disruption of the brain-spleen axis impairs monocyte-microglia communication and accelerates disease progression in a mouse model of amyloidosis

Alzheimer’s disease (AD) is characterized by a prolonged asymptomatic phase before cognitive decline emerges, yet the mechanisms driving symptom onset remain unclear. Here, we hypothesized that the transition from asymptomatic to symptomatic disease is linked to dysfunction of brain-immune communica...

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Auteurs principaux: Croese, Tommaso (Auteur) , Abellanas, Miguel A. (Auteur) , Polonsky, Hodaya (Auteur) , Arad, Michal (Auteur) , Peralta Ramos, Javier M. (Auteur) , Androsova, Yuliya (Auteur) , Riccitelli, Serena (Auteur) , Medina, Sedi (Auteur) , Palmas, Francesca (Auteur) , Strobel, Romano (Auteur) , Castellani, Giulia (Auteur) , Kviatcovsky, Denise (Auteur) , Phoebeluc-Colaiuta, Sarah (Auteur) , Adam, Miriam (Auteur) , Murad, Sama (Auteur) , Partney, Hannah (Auteur) , Kitsberg, Daniel (Auteur) , Dieter, Alexander (Auteur) , Salame, Tomer-Meir (Auteur) , Brandis, Alexander (Auteur) , Mehlman, Tevie (Auteur) , Singer, Oded (Auteur) , Rivlin-Etzion, Michal (Auteur) , Wiegert, Simon (Auteur) , Shaul, Yosef (Auteur) , Kobiler, Oren (Auteur) , Yizhar, Ofer (Auteur) , Habib, Naomi (Auteur) , Schwartz, Michal (Auteur)
Format: Article (Journal)
Langue:anglais
Publié: 19 June 2026
In: Nature Communications
Year: 2026, Volume: 17, Pages: 1-15
ISSN:2041-1723
DOI:10.1038/s41467-026-74253-z
Accès en ligne:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-026-74253-z
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-026-74253-z
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Notes sur l'auteur:Tommaso Croese, Miguel A. Abellanas, Hodaya Polonsky, Michal Arad, Javier M. Peralta Ramos, Yuliya Androsova, Serena Riccitelli, Sedi Medina, Francesca Palmas, Romano Strobel, Giulia Castellani, Denise Kviatcovsky, Sarah Phoebeluc-Colaiuta, Miriam Adam, Sama Murad, Hannah Partney, Daniel Kitsberg, Alexander Dieter, Tomer-Meir Salame, Alexander Brandis, Tevie Mehlman, Oded Singer, Michal Rivlin-Etzion, Simon Wiegert, Yosef Shaul, Oren Kobiler, Ofer Yizhar, Naomi Habib, Michal Schwartz
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Résumé:Alzheimer’s disease (AD) is characterized by a prolonged asymptomatic phase before cognitive decline emerges, yet the mechanisms driving symptom onset remain unclear. Here, we hypothesized that the transition from asymptomatic to symptomatic disease is linked to dysfunction of brain-immune communication. Retrograde neuronal tracing in the 5xFAD mouse model of amyloidosis reveals reduced brain-spleen connectivity at advanced disease stages. To probe the functional role of the brain-spleen axis in coping with disease, we denervated the splenic nerve at an early presymptomatic stage. This intervention accelerated cognitive decline, impaired splenic hematopoiesis, diminished monocyte recruitment to the brain, disrupted monocyte-microglia signaling networks, and reduced the transition of microglia from a homeostatic to a disease-associated (DAM) state. Conversely, enhancing splenic noradrenergic input increased hematopoiesis, restored monocyte homing to the brain, and delayed cognitive impairment. The protective role of splenic monocytes was independently validated in a retinal cytotoxic injury model, in which splenic denervation impairs post-insult survival of retinal ganglion cells. Together, these findings identify an active brain-spleen circuit in regulating monocyte recruitment, and establish peripheral monocytes as important drivers of microglial state transitions and disease progression.
Description:Online veröffentlicht: 19. Juni 2026, Artikelversion: 4. August 2026
Gesehen am 24.08.2026
Description matérielle:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-026-74253-z

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