Research Fellows Directory
Miss Karla Salgado-Puga
University of Southampton
The smells we encounter everyday are processed by the olfactory bulb, a brain area that is highly sensitive to changes in insulin/glucose metabolism. This means that diabetic patients often have a diminished sense of smell. Interestingly, smell is also affected in Alzheimer’s disease, in fact, the capacity to process and recognise smells is affected much earlier than memory functions in Alzheimer’s. But the relationship between disrupted glucose-insulin metabolism in the brain and the cellular and network mechanisms of odour-processing/recognition deficiencies in Alzheimer’s are not well understood.
The pathological hallmarks of Alzheimer’s disease are protein aggregates called: amyloid beta plaques and tau tangles, it is becoming clear that abnormal soluble forms of their amyloid beta and tau are toxic to neurons before they form these aggregates causing loss of neuronal connectivity and eventually neuronal death. Using transgenic mice to model early Alzheimer’s prior to protein aggregation, our project aims to understand the coupling of functions between olfactory bulb and hippocampus induced by the amyloid beta overproduction and tau dysfunction. We will focus on the study of glucose and insulin signalling disequilibrium as a driver of brain dysfunction at the interface of metabolism and neuronal network function.
By analysing the changes in neural function and metabolism early on in the disease process, we aim to identify and test potential molecular targets. The goal is to modify the progression of odour dysfunction and memory loss in our mouse model by rescuing the metabolic pathways that are disrupted by amyloid beta and tau. Our work could then be further developed pre-clinically and clinically in the future to prevent metabolic and neural network dysfunction in Alzheimer’s Disease.