TREM2-Deficient Microglia Attenuate Tau Spreading In Vivo.

Abstract

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.

• Authors: Audrey Lee-Gosselin, Nur Jury-Garfe, Yanwen You, Luke Dabin, Disha Soni, Sayan Dutta, Jean-Christophe Rochet, Jungsu Kim, Adrian L Oblak, Cristian A Lasagna-Reeves
• Journal: Cells (Cells) Vol. 12 Issue 12 (06 10 2023) ISSN: 2073-4409 [Electronic] Switzerland
• PMID: 37371067 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Membrane Glycoproteins
• Receptors, Immunologic
• tau Proteins
• Trem2 protein, mouse

Topics

• Alzheimer Disease (genetics, pathology)
• Membrane Glycoproteins (genetics)
• Microglia (metabolism)
• Receptors, Immunologic (genetics)
• Signal Transduction
• tau Proteins (genetics, metabolism)
• Tauopathies (pathology)
• Animals
• Mice