Humanized TREM2 mice show how the R47H gene variant affects microglia both directly and indirectly

The R47H variant of TREM2 is associated with impaired microglial activation and interaction with amyloid-β in a mouse model of Alzheimer's disease.

• The R47H variant of TREM2 triples the risk of Alzheimer's disease, according to genome-wide association studies.
• In mouse models of Alzheimer's, TREM2-deficient microglia do not proliferate or cluster around amyloid-β plaques.
• Transgenic mice expressing the common variant of TREM2 showed restored microglial activation in response to amyloid-β.
• The R47H variant did not restore this microglial response, indicating impaired TREM2 functionality.
• Soluble TREM2 was detected on neurons and plaques in mice with the common variant but not in those with the R47H variant.

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