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

Neuron. 2006 Dec 7;52(5):831-43. doi: 10.1016/j.neuron.2006.10.035.

Abstract

Beta amyloid (Abeta), 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 Abeta 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 Abeta-induced modification of synaptic structure and function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alphavirus Infections / genetics
  • Amyloid beta-Peptides / physiology*
  • Animals
  • Cells, Cultured
  • DNA / biosynthesis
  • DNA / genetics
  • Dendritic Spines / drug effects
  • Dendritic Spines / physiology*
  • Dendritic Spines / ultrastructure
  • Electrophysiology
  • Endocytosis / genetics
  • Endocytosis / physiology
  • Enzyme-Linked Immunosorbent Assay
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Image Processing, Computer-Assisted
  • Immunoblotting
  • Mutation / physiology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Neurons / physiology
  • Neurons / ultrastructure
  • Patch-Clamp Techniques
  • Phosphorylation
  • Rats
  • Receptors, AMPA / drug effects
  • Receptors, AMPA / genetics
  • Receptors, AMPA / physiology*
  • Receptors, Metabotropic Glutamate / biosynthesis
  • Receptors, Metabotropic Glutamate / genetics
  • Sindbis Virus / genetics
  • Synapses / drug effects
  • Synapses / physiology*
  • Synapses / ultrastructure
  • Transfection
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / physiology

Substances

  • Amyloid beta-Peptides
  • Excitatory Amino Acid Antagonists
  • Receptors, AMPA
  • Receptors, Metabotropic Glutamate
  • DNA
  • p38 Mitogen-Activated Protein Kinases