The Role of TREM2 in Traumatic Brain Injury Induced Tauopathy
Annual rept. 15 Aug 2014-14 Aug 2015
CLEVELAND CLINIC OH
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Traumatic brain injury TBI promotes several Alzheimers 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 TREM2monocytesmicroglia can be targeted in future studies.
- Medicine and Medical Research