TREM2 deficiency exacerbates tau pathology through dysregulated kinase signaling in a mouse model of tauopathy.

Title

TREM2 deficiency exacerbates tau pathology through dysregulated kinase signaling in a mouse model of tauopathy.

Creator

Bemiller Shane M; McCray Tyler J; Allan Kevin; Formica Shane V; Xu Guixiang; Wilson Gina; Kokiko-Cochran Olga N; Crish Samuel D; Lasagna-Reeves Cristian A; Ransohoff Richard M; Landreth Gary E; Lamb Bruce T

Publisher

Molecular neurodegeneration

Date

2017
2017-10

Description

BACKGROUND: Genetic variants of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) confer increased risk of developing late-onset Alzheimer's Disease (LOAD) and other neurodegenerative disorders. Recent studies provided insight into the multifaceted roles of TREM2 in regulating extracellular beta-amyloid (Abeta) pathology, myeloid cell accumulation, and inflammation observed in AD, yet little is known regarding the role of TREM2 in regulating intracellular microtubule associated protein tau (MAPT; tau) pathology in neurodegenerative diseases and in AD, in particular. RESULTS: Here we report that TREM2 deficiency leads to accelerated and exacerbated hyperphosphorylation and aggregation of tau in a humanized mouse model of tauopathy. TREM2 deficiency also results, indirectly, in dramatic widespread dysregulation of neuronal stress kinase pathways. CONCLUSIONS: Our results suggest that deficiency of microglial TREM2 leads to heightened tau pathology coupled with widespread increases in activated neuronal stress kinases. These findings offer new insight into the complex, multiple roles of TREM2 in regulating Abeta and tau pathologies.

Subject

*Alzheimers disease; *Immunity; *Inflammation; *Tauopathy; *TREM2; Animal; Animals; Disease Models; Humans; Immunologic/*deficiency; Inbred C57BL; Membrane Glycoproteins/*deficiency; Mice; Microglia/metabolism; Protein Kinases/*metabolism; Receptors; Signal Transduction/physiology; tau Proteins/*metabolism; Tauopathies/metabolism/*pathology; Transgenic

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

74–74

Issue

1

Volume

12

Citation

Bemiller Shane M; McCray Tyler J; Allan Kevin; Formica Shane V; Xu Guixiang; Wilson Gina; Kokiko-Cochran Olga N; Crish Samuel D; Lasagna-Reeves Cristian A; Ransohoff Richard M; Landreth Gary E; Lamb Bruce T, “TREM2 deficiency exacerbates tau pathology through dysregulated kinase signaling in a mouse model of tauopathy.,” NEOMED Bibliography Database, accessed October 17, 2021, https://neomed.omeka.net/items/show/4868.

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