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Receptor signaling cascade-mediating Alzheimer's disease synapse damage by Aβ oligomers. Schematic illustrates the role of mGluR5 in linking cell surface Aβo–PrPC complexes to intracellular Fyn/Pyk2 and synaptic loss. Proteins are clustered in the PSD and alter NMDARs, calcium, and protein translation. Pyk2(PTK2B) variation is a verified genetic risk for late-onset AD. Tau plays a role in localizing Fyn. Aberrant PrPC–mGluR5–Fyn–Tau signaling leads to synaptic malfunction and loss.
