Professor Sarah King
Inhibitory circuits influencing addiction
Healthy Ageing: Understanding the impact of risk and resilience factors on brain and behaviour
Most therapeutic strategies for treating Alzheimer’s disease have focused on cures. However waiting for the pathology to set in may be too late. Prevention would be a more effective strategy. Carrying an APOE4 allele is the greatest risk factor for Alzheimer’s disease aside from age. However studies in my lab using targeted replacement mice have found little difference on cognitive performance across the lifespan with shifted APOE genotype alone. Our working hypothesis is that the APOE4 risk only becomes apparent in the presence of other risk factors, e.g. diet, exercise, social isolation. Projects will use mice to study the behavioural and neurobiological impact of cumulative risk factors to identify critical windows in the lifespan, and interventions that might protect the brain from cognitive decline and dementia.
Key references
- Grant summary of work on Social Isolation / Interaction:
- Multi-hit hypothesis:
*Steele OG, Stuart AC, Minkley L, Shaw K, Bonnar O, Anderle S, Penn AC, Rusted J, Serpell L, Hall C & King SL (2022). A multi-hit hypothesis for an APOE4-dependent pathophysiological state. European Journal of Neuroscience, 1– 40. https://doi.org/10.1111/ejn.15685
- Risk factors for Alzheimer’s:
Livingston, Gill et al. Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission The Lancet, Volume 404, Issue 10452, 572 – 628. https://doi.org/10.1016/S0140-6736(24)01296-0
Visit the Behavioural and Clinical Neuroscience website for more information.