Deleterious Effects of Amyloid β Oligomers Acting as an Extracellular Scaffold for mGluR5
Abstract
Soluble oligomers of amyloid b (Ab) play a role in the memory impairment characteristic of Alzheimer's disease. Acting as pathogenic ligands, Ab oligomers bind to particular synapses and perturb their function, morphology, and maintenance. Events that occur shortly after oligomer binding have been investigated here in live hippocampal neurons by single particle tracking of quantum dot-labeled oligomers and synaptic proteins. Membrane-attached oligomers initially move freely, but their diffusion is hindered markedly upon accumulation at synapses. Concomitantly, individual metabotropic glutamate receptors (mGluR5) manifest strikingly reduced lateral diffusion as they become aberrantly clustered. This clustering of mGluR5 elevates intracellular calcium and causes synapse deterioration, responses prevented by an mGluR5 antagonist. As expected, clustering by artificial crosslinking also promotes synaptotoxicity. These results reveal a mechanism whereby Ab oligomers induce the abnormal accumulation and overstabilization of a glutamate receptor, thus providing a mechanistic and molecular basis for Ab oligomer-induced early synaptic failure.
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BibTeX
@article{renner2026deleterious,
title = {{Deleterious Effects of Amyloid β Oligomers Acting as an Extracellular Scaffold for mGluR5}},
author = {Marianne Renner and Pascale N Lacor and Pauline T Velasco and Jian Xu and Anis Contractor and William L Klein and Antoine Triller},
journal = {Neuron},
year = {2026},
month = oct,
doi = {10.1016/j.neuron.2010.04.029},
url = {https://hal.science/hal-05782854v1},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Deleterious Effects of Amyloid β Oligomers Acting as an Extracellular Scaffold for mGluR5
AU - Marianne Renner
AU - Pascale N Lacor
AU - Pauline T Velasco
AU - Jian Xu
AU - Anis Contractor
AU - William L Klein
AU - Antoine Triller
PY - 2026
DA - 2026/10/12
JO - Neuron
DO - 10.1016/j.neuron.2010.04.029
UR - https://hal.science/hal-05782854v1
AB - Soluble oligomers of amyloid b (Ab) play a role in the memory impairment characteristic of Alzheimer's disease. Acting as pathogenic ligands, Ab oligomers bind to particular synapses and perturb their function, morphology, and maintenance. Events that occur shortly after oligomer binding have been investigated here in live hippocampal neurons by single particle tracking of quantum dot-labeled oligomers and synaptic proteins. Membrane-attached oligomers initially move freely, but their diffusion is hindered markedly upon accumulation at synapses. Concomitantly, individual metabotropic glutamate receptors (mGluR5) manifest strikingly reduced lateral diffusion as they become aberrantly clustered. This clustering of mGluR5 elevates intracellular calcium and causes synapse deterioration, responses prevented by an mGluR5 antagonist. As expected, clustering by artificial crosslinking also promotes synaptotoxicity. These results reveal a mechanism whereby Ab oligomers induce the abnormal accumulation and overstabilization of a glutamate receptor, thus providing a mechanistic and molecular basis for Ab oligomer-induced early synaptic failure.
SN - 0896-6273
ER -