AMPAR removal underlies Aβ-induced synaptic depression and dendritic spine loss

Beta amyloid (A beta), a peptide generated from the amyloid precursor protein (APP) by neurons, is widely believed to underlie the pathophysiology of Alzheimer's disease. Recent studies indicate that this peptide can drive loss of surface AMPA and NMDA type glutamate receptors. We now show that A beta employs signaling pathways of long-term depression (LTD) to drive endocytosis of synaptic AMPA receptors. Synaptic removal of AMPA receptors is necessary and sufficient to produce loss of dendritic spines and synaptic NIVIDA responses. Our studies indicate the central role played by AMPA receptor trafficking in A beta-induced modification of synaptic structure and function.