Format

Send to

Choose Destination
Mol Neurodegener. 2017 Oct 16;12(1):74. doi: 10.1186/s13024-017-0216-6.

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

Author information

1
Department of Neurosciences, The Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA. sbemille@iu.edu.
2
Kent State University, School of Biomedical Sciences, Kent, OH, USA. sbemille@iu.edu.
3
Indiana University School of Medicine Stark Neuroscience Research Institute, Indianapolis, IN, USA. sbemille@iu.edu.
4
Indiana University School of Medicine Stark Neuroscience Research Institute, Indianapolis, IN, USA.
5
Department of Neurosciences, Case Western Reserve University, Cleveland, USA.
6
Department of Neurosciences, The Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
7
Department of Neurosciences, Northeastern Ohio Medical University, Rootstown, OH, USA.
8
Department of Neurosciences, The Ohio State University, Columbus, OH, USA.
9
Biogen IDEC, Boston, MA, USA.
10
Department of Neurosciences, The Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA. btlamb@iu.edu.
11
Indiana University School of Medicine Stark Neuroscience Research Institute, Indianapolis, IN, USA. btlamb@iu.edu.

Abstract

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 β-amyloid (Aβ) 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 Aβ and tau pathologies.

KEYWORDS:

Alzheimers disease; Immunity; Inflammation; TREM2; Tauopathy

PMID:
29037207
PMCID:
PMC5644120
DOI:
10.1186/s13024-017-0216-6
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center