Format

Send to

Choose Destination
Neurobiol Aging. 2015 Dec;36(12):3176-3186. doi: 10.1016/j.neurobiolaging.2015.08.019. Epub 2015 Aug 24.

Silencing of TREM2 exacerbates tau pathology, neurodegenerative changes, and spatial learning deficits in P301S tau transgenic mice.

Author information

1
Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
2
Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, People's Republic of China; Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, People's Republic of China. Electronic address: dr.tanlan@163.com.
3
Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
4
Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, People's Republic of China.
5
Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Pathophysiology, Nanjing Medical University, Nanjing, People's Republic of China.
6
Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People's Republic of China. Electronic address: zhangyingdong@aliyun.com.
7
Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA, USA. Electronic address: yu-jintai@163.com.

Abstract

Tau pathology is a pathological hallmark for several neurodegenerative diseases including Alzheimer's disease and frontotemporal dementia. As a novel susceptibility gene for these 2 diseases, triggering receptor expressed on myeloid cells 2 (TREM2) gene encodes an immune receptor that is uniquely expressed by microglia. Recently, a correlation between TREM2 expression and hyperphosphorylated tau has been revealed in the brain of Alzheimer's disease patients, suggesting a potential association between TREM2 and tau pathology. However, the role of TREM2 in tau pathology remains unclear thus far. Herein, using P301S mice, we showed that TREM2 was upregulated in microglia during disease progression. Silencing of brain TREM2 exacerbated tau pathology in P301S mice. This exacerbation might be attributed to neuroinflammation-induced hyperactivation of tau kinases. Additionally, more severe neurodegenerative changes and spatial learning deficits were observed following TREM2 silencing. Our results imply that TREM2 attenuates tau kinase activity through restriction of neuroinflammation, and thus protects against tau pathology. These findings further suggest that TREM2 may represent as a potential therapeutic target for tau-related neurodegenerative diseases.

KEYWORDS:

Alzheimer's disease; Frontotemporal dementia; Microglia; Neurodegeneration; Spatial cognitive deficits; TREM2; Tau pathology

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center