Figure 2.

Alzheimer's related modulation of GluA1 and consequent pathology. A, M1 receptor activation can rescue cognitive impairment through modulation of GluA1 S845 phosphorylation and downstream incorporation with PSD‐95, a pathway that is compromised by Aβ aggregation. B, Aβ reduces PSD‐95, a protein involved in recruiting and anchoring glutamate receptor subunits to the post‐synaptic density. In agreement, we observed early reductions in surface expression of glutamate receptor subunit GluA1. C. Aβ oligomers cause mislocalization of tau protein to the dendritic spines. There, calcineurin‐mediated dephosphorylation of GluA1 S845 triggers a pathological cascade or rapid AMPAR insertion and acute neurotoxicity. D, Aβ oligomers impair synaptic function by decreasing the amplitude of mEPSCs