The gain-of-function TREM2-T96K mutation increases risk for Alzheimer's disease by impairing microglial function.

Pilat DJ, Le H, Prokopenko D, Lin CJ, Eimer WA et al.

Neuron 2026

We previously reported that T96K is a gain-of-function mutation in TREM2 based on its ability to increase ligand-dependent activation. Here, we show that TREM2

6 Figures Extracted

Figure 3.

Trem2 T96K leads to reduced total area of Iba1 + microglia and limits microglial association with Aβ plaques in 5xFAD mice in a sex-dependent mann...

Figure 4.

The T96K mutation reduces levels of soluble Trem2 in female 5xFAD mice and human microglial cells and impairs Aβ42 uptake in knockin microglial cell...

Figure 5.

Trem2 T96K mutation leads to a sex-specific reduction in total area of phagocytic microglia in 5xFAD mice (A–F) (A and B) Brain sections were label...

Figure 6.

Trem2 T96K results in the suppression of the DAM gene signature and downregulation of inflammatory pathways in female 5xFAD mice (A) UMAP plot of 9...

Figure 7.

Trem2 T96K mutation reduces total area of CD11c + microglia and Itgax expression levels in female 5xFAD mice (A and B) Brain sections were label...

Figure 8.

Trem2 T96K leads to defects in the DAM trajectories of microglia in female 5xFAD mice (A) UMAP plot of 77,666 microglial cells, colored by unsuperv...