Soluble oligomers of amyloid-β peptide disrupt membrane trafficking of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor contributing to early synapse dysfunction

Topic: Brain proteins, microglia and lab models

β-Amyloid (Aβ), a peptide generated from the amyloid precursor protein, is widely believed to underlie the pathophysiology of Alzheimer disease (AD). Emerging evidences suggest that soluble Aβ oligomers adversely affect synaptic function, leading to cognitive failure associated with AD. The Aβ-induced synaptic dysfunction has been attributed to the synaptic removal of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors (AMPARs).

Key findings

• Emerging evidences suggest that soluble Aβ oligomers adversely affect synaptic function, leading to cognitive failure associated with AD.
• The Aβ-induced synaptic dysfunction has been attributed to the synaptic removal of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors (AMPARs).
• However, the molecular mechanisms underlying the loss of AMPAR induced by Aβ at synapses are largely unknown.
• In this study we have examined the effect of Aβ oligomers on phosphorylated GluA1 at serine 845, a residue that plays an essential role in the trafficking of AMPARs toward extrasynaptic sites and the subsequent delivery to synapses during synaptic plasticity events.

Why it matters

This laboratory study found that soluble amyloid-beta oligomers disrupt membrane trafficking of AMPA receptors, contributing to early synapse dysfunction. It describes a mechanism of synaptic damage and does not test any treatment, cure, or prevention.

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Study details

• Evidence strengthLow

Read the original

• DOI: 10.1074/jbc.m111.227504
• PubMed: 21665950
• Original source →
• Free full text: Journal of Biological Chemistry →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

@article{minanomolina2011-21665950,
  author  = {Miñano-Molina, A. J. and España, J. and Martín, E. and Barneda-Zahonero, B. and Fadó, R. and Solé, M. and Trullás, R. and Saura, C. A. and others},
  title   = {{Soluble oligomers of amyloid-β peptide disrupt membrane trafficking of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor contributing to early synapse dysfunction}},
  journal = {The Journal of biological chemistry},
  year    = {2011},
  doi     = {10.1074/jbc.m111.227504},
  pmid    = {21665950},
  url     = {https://doi.org/10.1074/jbc.m111.227504}
}

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Abeta toxicity in Alzheimer's disease: globular oligomers (ADDLs) as new vaccine and drug targets Neurochemistry international · 2002-11-01 · usefulness score 45/100 · Mild cognitive impairment

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