Amyloid-β-Driven Synaptic Deficits Are Mediated by Synaptic Removal of GluA3-Containing AMPA Receptors.

ABSTRACT: The detrimental effects of oligomeric amyloid-β (Aβ) on synapses are considered the leading cause for cognitive deficits in Alzheimer's disease. However, through which mechanism Aβ oligomers impair synaptic structure and function remains unknown. Here, we used electrophysiology and amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) imaging on mouse and rat neurons to demonstrate that GluA3 expression in neurons lacking GluA3 is sufficient to resensitize their synapses to the damaging effects of Aβ, indicating that GluA3-containing AMPARs at synapses are necessary and sufficient for Aβ to induce synaptic deficits. We found that Aβ oligomers trigger the endocytosis of GluA3 and promote its translocation toward endolysosomal compartments for degradation. Mechanistically, thes

SUBMITTER: Reinders NR 

PROVIDER: S-EPMC11867010 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature