Intracellular oligomeric amyloid-beta rapidly regulates GluA1 subunit of AMPA receptor in the hippocampus

Daniel J Whitcomb, Ellen L Hogg, Philip Regan, Thomas Piers, Priyanka Narayan, Garry Whitehead, Bryony L Winters, Dong-Hyun Kim, Eunjoon Kim, Peter St George-Hyslop, David Klenerman, Graham L Collingridge, Jihoon Jo, Kwangwook Cho

Research output: Contribution to journalArticlepeer-review

83 Citations (SciVal)


The acute neurotoxicity of oligomeric forms of amyloid-β 1-42 (Aβ) is implicated in the pathogenesis of Alzheimer's disease (AD). However, how these oligomers might first impair neuronal function at the onset of pathology is poorly understood. Here we have examined the underlying toxic effects caused by an increase in levels of intracellular Aβ, an event that could be important during the early stages of the disease. We show that oligomerised Aβ induces a rapid enhancement of AMPA receptor-mediated synaptic transmission (EPSC(A)) when applied intracellularly. This effect is dependent on postsynaptic Ca(2+) and PKA. Knockdown of GluA1, but not GluA2, prevents the effect, as does expression of a S845-phosphomutant of GluA1. Significantly, an inhibitor of Ca(2+)-permeable AMPARs (CP-AMPARs), IEM 1460, reverses the increase in the amplitude of EPSC(A). These results suggest that a primary neuronal response to intracellular Aβ oligomers is the rapid synaptic insertion of CP-AMPARs.

Original languageEnglish
Article number10934
JournalScientific Reports
Publication statusPublished - 9 Jun 2015


  • Alzheimer Disease/metabolism
  • Amyloid beta-Peptides/metabolism
  • Animals
  • Calcium/metabolism
  • Cyclic AMP-Dependent Protein Kinases/metabolism
  • Cytoplasm/metabolism
  • Hippocampus/metabolism
  • Male
  • Neurons/metabolism
  • Phosphorylation/physiology
  • Protein Transport/physiology
  • Rats
  • Rats, Wistar
  • Receptors, AMPA/metabolism
  • Receptors, Glutamate/metabolism
  • Synapses/metabolism


Dive into the research topics of 'Intracellular oligomeric amyloid-beta rapidly regulates GluA1 subunit of AMPA receptor in the hippocampus'. Together they form a unique fingerprint.

Cite this