What happens to neuronal circuits in Alzheimer’s Disease?

Alzheimer’s disease (AD) is a fatal brain disease with a massive societal impact. Identifying effective treatments for Alzheimer’s disease (AD) has proven extremely challenging and has instigated a recent shift in AD research focus towards the earliest disease-initiating cellular processes. A key insight has been that of an increase in soluble amyloid-beta in early AD that is causally linked to neuronal and circuit hyperexcitability. However, other peptides that accumulate in the AD brain, including tau, exhibit complex opposing effects on circuit dynamics (e.g. hypoexcitability). In this presentation, I will review the latest evidence base pertaining to hyper- and hypoexcitability in AD, and signpost potential pathways in which related neuronal dysfunction may be leveraged to guide biomarker identification and therapy in the disorder.