AMPAR Removal Underlies Aβ-Induced Synaptic Depression and Dendritic Spine Loss

Helen Hsieh, Jannic Boehm, Chihiro Sato, Takeshi Iwatsubo, Taisuke Tomita, Sangram Sisodia, Roberto Malinow

Research output: Contribution to journalArticlepeer-review

873 Scopus citations

Abstract

Beta amyloid (Aβ), 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 Aβ 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 NMDA responses. Our studies indicate the central role played by AMPA receptor trafficking in Aβ-induced modification of synaptic structure and function.

Original languageEnglish
Pages (from-to)831-843
Number of pages13
JournalNeuron
Volume52
Issue number5
DOIs
StatePublished - Dec 7 2006

Keywords

  • HUMDISEASE
  • MOLNEURO
  • SYSBIO

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