The Role of TREM2 in Traumatic Brain Injury Induced Tauopathy
Abstract
Traumatic brain injury (TBI) promotes several Alzheimer's disease (AD)-like pathological features including accumulation of microtubule-associated protein tau (MAPT) within neurons; however, genetic risk factors that link TBI and MAPT pathology remain unclear, The recent identification of mutations in Triggering Receptor Expressed on Myeloid cells 2 (TREM2) that are associated with dementia and AD enables studies to examine the relationship between TBI, inflammation, TREM2 and development of AD-like pathologies expressed in a mouse Mapt knockout background19. We have previously shown that TBI causes enhanced MAPT phosphorylation and aggregation with heightened macrophage activation in hTau mice at 3 DPI suggesting that there is a correlation between MAPT pathology and alterations in macrophage activation following TBI. We hypothesize that up-regulation of TREM2 within monocytes and microglia observed following TBI plays a protective role in the development of MAPT pathologies. These studies will develop novel resources and models to identify potential genetic factors regulating the TBI-AD connection as well as pathways downstream of TREM2 that may impact TBI induced MAPT pathology and neurodegeneration. Indeed, this work is particularly relevant for high risk TBI populations such as soldiers, as potential therapies focused on TREM2/monocytes/microglia can be targeted in future studies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2015
- Accession Number
- ADA626168
Entities
People
- Bruce T. Lamb