Plaque contact and unimpaired Trem2 is required for the microglial response to amyloid pathology

In 18-month-old APPknockin mice, 38 out of 55 plaque-induced genes (PIGs) show increased expression in microglia touching plaques.

• Microglial upregulation of certain genes is observed primarily in those cells directly contacting plaques.
• In APPTrem2mice, the upregulation of seven PIGs, including Trem2, is prevented.
• TREM2-dependent genes are linked to processes related to clearing cellular debris and managing waste.
• A decrease in markers for phagocytosis and an increase in small plaque density are noted in Trem2-mutated mice.
• Despite the R47H mutation limiting Trem2 gene expression, TREM2 protein levels and microglial density near plaques are still slightly elevated.
• Effective microglial response to amyloid pathology requires both direct contact with plaques and functional TREM2.

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