PhD Position: Finding the Missing Link between Aβ Exposure and Inhibitory Synaptic Defects

One of the main reasons that there is no treatment for Alzheimer’s disease (AD) is that cellular mechanisms of the disease onset and progression are not well understood. AD is a slowly progressing disease. Long before cognitive and behavioural symptoms occur, the level of Aβ oligomers in the brain are slowly rising, causing synaptic defects and network hyperexcitability. Hyperexcitable networks have been widely observed in AD patients and can be reproduced in a wide range of AD mouse models with progressing Aβ levels. Preventing or delaying hyperexcitability can delay or prevent cognitive impairments, indicating that hyperexcitability in early AD stages is a crucial factor in the progression of the disease. An increasing number of studies (including from our lab: Ruiter et al, J Alz Dis 2020) are demonstrating that inhibitory circuits are specifically vulnerable to Aβ in the brain, which could underlie the enhanced excitability in neuronal networks observed at early AD stages. Howev...