In summary, we show that mGluR5, which functions as a membrane bound receptor scaffolds for both PrPc and Aβ oligomers [17-19], functions to transduce Aβ oligomer-mediated signals as alterations in intracellular Ca2+ signaling, as well as FMRP/Aβ mediated pathological signaling in the APPswe/PS1∆E9 mouse model of AD. Here, PRNP is linked to Alzheimer disease.