Topic: Aβ oligomers

During early stages of Alzheimer’s disease (AD) gradual accumulation and aggregation of Aβ oligomers (AβO) occurs prior to cognitive decline. This preclinical stage of AD is further characterized by synaptic dysfunction and network hyperexcitability. We recently discovered that 24-hour treatment of AβO​​​​​ to hippocampal slices impairs release at GABAergic synapses, most prominently at dendritic inhibitory synapses. This suggests that inhibitory synapses are particularly vulnerable to AβO toxicity.We currently use advanced imaging approaches in vitro to further investigate the mechanisms that

Central insulin resistance is a typical trait associated with premature ageing and is shown in neurological illnesses such as Alzheimer’s disease (AD) in its early stages. In this sense, the (phosphoinositide 3 kinase)/Akt pathway mediates insulin signalling in the brain, where defective insulin signalling is a risk factor for developing AD. Several lines of evidence show that integrated coordination of neuronal responses through the PI3K /Akt pathway in the brain has a significant functional impact on key events that are negatively affected in AD. Moreover, the PIK3/Akt pathway is crucial in

A major component of Alzheimer's disease pathology is the accumulation of amyloid-β (Aβ), a peptide that is known to weaken synaptic transmission. Whereas both AMPA receptor (AMPAR) and NMDA receptor (NMDAR) currents are affected by Aβ oligomers, not all synapses are equally vulnerable to the toxic effects of Aβ. We set out to elucidate the roles of the different AMPAR and NMDAR subunits in synapse susceptibility to Aβ. Whole-cell patch clamp recordings were performed in hippocampal CA1 neurons that overexpress Aβ oligomers. Variance analysis was used to disentangle whether this decreased syna

Alzheimer's disease (AD) is characterized by an early hippocampus hyperactivity triggered by Aβ oligomers (Aβo) in humans and AD mouse models, followed by hypoactivity and synaptic loss occurring before cognitive decline. GWAS identified PTK2B gene encoding for Pyk2, a tyrosine kinase involved in synaptic plasticity, as a new AD risk factor. Several studies have validated Pyk2 involvement in AD pathophysiology, but its exact role is still debated due to conflicting results. The objective of this project is to decipher the role of Pyk2 in synaptic dysfunctions observed in this disease. We first