An Unbalanced Synaptic Transmission: Cause or Consequence of the Amyloid Oligomers Neurotoxicity?

Amyloid-beta (A beta) 1-40 and 1-42 peptides are key mediators of synaptic and cognitive dysfunction in Alzheimer's disease (AD). Whereas in AD, AP is found to act as a pro-epileptogenic factor even before plaque formation, amyloid pathology has been detected among patients with epilepsy with increased risk of developing AD. Among A beta aggregated species, soluble oligomers are suggested to be responsible for most of A beta's toxic effects. A beta oligomers exert extracellular and intracellular toxicity through different mechanisms, including interaction with membrane receptors and the formation of ion-permeable channels in cellular membranes. These damages, linked to an unbalance between excitatory and inhibitory neurotransmission, often result in neuronal hyperexcitability and neural circuit dysfunction, which in turn increase A beta deposition and facilitate neurodegeneration, resulting in an A beta-driven vicious loop. In this review, we summarize the most representative literature on the effects that oligomeric A beta induces on synaptic dysfunction and network disorganization.

Automated summary

Oligomeric A beta proteins exert toxicity through interaction with membrane receptors and formation of ion-permeable channels, affecting synaptic function and network structure.