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TREM2 variants: new keys to decipher Alzheimer disease pathogenesis

Abstract

Genome-wide association studies have identified rare variants of the gene that encodes triggering receptor expressed on myeloid cells 2 (TREM2) — an immune receptor that is found in brain microglia — as risk factors for non-familial Alzheimer disease (AD). Furthermore, animal studies have indicated that microglia have an important role in the brain response to amyloid-β (Aβ) plaques and that TREM2 variants may have an impact on such a function. We discuss how TREM2 may control the microglial response to Aβ and its impact on microglial senescence, as well as the interaction of TREM2 with other molecules that are encoded by gene variants associated with AD and the hypothetical consequences of the cleavage of TREM2 from the cell surface.

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Figure 1: TREM2 signalling pathways.
Figure 2: Potential models of TREM2 function in microglial response to Alzheimer disease.

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Acknowledgements

The authors thank S. Gilfillan for helpful comments. M.C. is supported by the US National Institutes of Health (NIH) 1RF1AG051485-01 and the Cure Alzheimer disease Fund. Y.W. is supported by the Lilly Innovation Fellowship Award (Eli Lilly and Company).

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Correspondence to Marco Colonna.

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Y.W. is an employee of Eli Lilly & Co. M.C. declares no competing interests.

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Colonna, M., Wang, Y. TREM2 variants: new keys to decipher Alzheimer disease pathogenesis. Nat Rev Neurosci 17, 201–207 (2016). https://doi.org/10.1038/nrn.2016.7

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