Our research investigates how pathogenic forms of amyloid-β impair synaptic function and plasticity in Alzheimer’s disease. Prof Hu’s work demonstrated that the amyloid-β dimer is the smallest synaptotoxic form capable of disrupting synaptic plasticity, helping to define the molecular species responsible for early synaptic dysfunction.

We investigate how extracellular tau disrupts synaptic function and the molecular pathways that could be targeted therapeutically. Recent work has demonstrated that the microtubule-binding region of tau mediates its synaptotoxic effects and that the glutamate receptor system and integrated stress response as potential therapeutic targets for protecting synaptic function in neurodegenerative disease.

A major focus of our laboratory is understanding the mechanisms of synaptic plasticity underlying learning and memory. We have developed reliable methods for inducing hippocampal long-term depression (LTD) in vivo, using both electrical stimulation and optogenetic approaches. Together with the study of long-term potentiation (LTP), these methods allow us to investigate both major forms of synaptic plasticity and how they are altered in neurodegenerative disease.