Glucocorticoids, synaptic plasticity and Alzheimer's disease
Igor Klyubin, Tomáš Ondrejčák, Neng‐Wei Hu, Michael J. Rowan
Abstract
How excessive stress and cortisol exposure predispose people to clinical Alzheimer's disease (AD) is a matter of great potential medical impact. We discuss recent findings regarding the mechanism of persistent disruption of synaptic plasticity and related cognition caused by hypothalamic–pituitary–adrenal (HPA) axis dysregulation in this context. Growing evidence supports the view that in addition to the pathogenic proteins amyloid beta and tau driving HPA and hence synaptic plasticity disruption, excess glucocorticoid receptor activation promotes amyloidosis and tauopathy-mediated synaptotoxicity. The critical role of glia-mediated pro-inflammatory processes in the impairment of synaptic and cognitive function by stress is also delineated. Combining (non)-pharmacological interventions that target glucocorticoid-synaptic plasticity pathways with more classical anti-tau and anti-amyloid strategies to treat early AD prior to dementia onset certainly warrants further investigation.