Dietary Methionine Restriction as a Means to Combat Cognitive Dysfunction in a Mouse Model of Alzheimer’s Disease

Supervisors: Dr Mirela Delibegovic, Prof Bettina Platt and Dr Nimesh Mody

Recent evidence suggests that there is a close link between Alzheimer’s disease (AD) and type 2 diabetes (T2DM) in humans. A major cause of T2DM is impaired insulin action or insulin resistance, which is commonly associated with obesity. Moreover, ageing is associated with an increased incidence of these diseases. In this project we aim to analyse if improvements in insulin sensitivity and/or age-induced neuro-degeneration will prevent or postpone cognitive deficits associated with AD genotype. We will use a newly established AD mouse model generated at the University of Aberdeen. These mice display a pathophysiology reminiscent of early, prodromal AD consisting of intraneuronal build-up of APP/A and tau that appear prior to plaque and tangle deposition; alterations in brain metabolism prior to cognitive impairment and finally age-related cognitive deficits. The student will receive excellent training in: in vivo metabolic phenotyping (eg glucose and insulin tolerance tests, blood serum cytokine/adipokine analyses, temperature recordings, DEXA scanning), cognitive and behavioural phenotyping (eg Y maze, Phenotyper), cell isolation and sorting techniques (eg FACS analysis), sterile cell culture maintenance and stimulations (eg primary neurons and neuronal cell lines) and in biochemical analysis (Western blotting, ELISAs). The student will also be trained in live cell and confocal microscopy as well as immunohistochemistry.