Trem2 Y38C mutation and loss of Trem2 impairs neuronal synapses in adult mice

Abstract

Our findings provide in vivo evidence that Trem2 Y38C disrupts normal TREM2 functions. Trem2^Y38C/Y38C and Trem2^-/- mice demonstrated altered gene expression, changes in microglia morphology, loss of synaptic proteins and reduced hippocampal synaptic plasticity at 6 months in absence of any pathological triggers like amyloid. This suggests TREM2 impacts neuronal functions providing molecular insights on the predisposition of individuals with TREM2 variants resulting in presenile dementia.