Several risk factors for Alzheimer’s disease including diabetes and midlife obesity are age-dependent and have an obvious metabolic component resulting in impaired glucose metabolism. This can lead to altered brain protein O-GlcNAcylation, a glucose dependent post-translational modification. In addition, pre-clinical models of these life-style risk factors for Alzheimer’s disease demonstrate impaired cognition The aim of the study is to improve our understanding of how type 2 diabetes and midlife obesity increase the risk for developing Alzheimer’s. To do this, the project will (i) determine the age-dependent impact of lifestyle associated risk factors on cognition, and (ii) to determine a glucose-dependent molecular signature of modifiable risk factors for Alzheimer’s disease . Techniques and Methodology Behavioural and cognitive testing, proteomic analysis, protein purification, SDS-PAGE.
Impact on Alzheimer’s research Alzheimer’s is a multi-causal disease that manifests in a common neuropathological and clinical phenotype. At the end of this study we will identify common molecular pathways from two associated risk factors for developing Alzheimer’s, diabetes and midlife obesity and so identify novel disease pathways and molecular mechanisms for future investigations into therapeutic interventions.