@article{27f0bbaa40494e42ad995ad6182f4c74,
title = "AMPAR Removal Underlies Aβ-Induced Synaptic Depression and Dendritic Spine Loss",
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.",
keywords = "HUMDISEASE, MOLNEURO, SYSBIO",
author = "Helen Hsieh and Jannic Boehm and Chihiro Sato and Takeshi Iwatsubo and Taisuke Tomita and Sangram Sisodia and Roberto Malinow",
note = "Funding Information: We thank Graziella DiCristo, Emiliano Verde, and members of the Malinow laboratory for helpful discussions; William Benjamin for careful reading of the manuscript; and Nancy Dawkins for expert technical assistance. We thank Takeda Pharmaceutical Company for Aβ enzyme-linked immunosorbent assay and Richard L. Huganir for providing us with anti-phospho-GluR2(S880). This work was supported by grants from the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO) (T.I. and T.T.), the Ministry of Education, Science, Culture and Sports for the 21st Century Center of Excellence Program, Japan (T.I. and T.T.), the Fidelity Foundation (R.M.), National Institutes of Health (AG021494, S.S.), the Alzheimer's Association (J.B.), and the National Institute of Neurological Disorders and Stroke (NRSA, H.H.). ",
year = "2006",
month = dec,
day = "7",
doi = "10.1016/j.neuron.2006.10.035",
language = "English",
volume = "52",
pages = "831--843",
journal = "Neuron",
issn = "0896-6273",
number = "5",
}