Though previous studies have demonstrated that a broad conceptual role of mGluR5 antagonism is the restoration of memory function in TG mouse models of Alzheimer’s disease (e.g. Hamilton et al., 2016), our study provides a framework for these effects: the aberrant activation of mGluR5 impairing postsynaptic mAChR function, where through blocking mGluR5, postsynaptic mAChR function and object recognition memory in Alzheimer’s disease models can be restored. Here, GRM5 is linked to early-onset autosomal dominant Alzheimer disease.