A Targeted Brain Proteomic Study Linking Diet, Ageing and Cognition

Supervisors: Dr Lynda Williams, Dr Rosamund Langston (University of Dundee) & Dr Fiona Campbell

We have recently identified that the gene serpinA3n encoding the acute phase protein alpha-1 antichymotrypsin (aACT) is up-regulated by a diet high in saturated fat and sugar in the hypothalamus and hippocampus of the brain in a widely used mouse model of diet induced obesity and insulin insensitivity (1). Insulin insensitivity and neuronal inflammation are related to cognitive decline. SerpinA3n gene expression also increases with age in mice (Williams et al unpublished results). The function of the protein aACT in the brain has not been completely elucidated but aACT is known to form complexes with apolipoprotein E (ApoE) and protein amyloid β and is an integral component of the plaques found in Alzheimer's disease (2).

The present project seeks to investigate the role of aACT in the rodent brain. The fate and function of aACT in the brain will be identified using a targeted proteomic approach including co-immunoprecipitation and mass spectroscopy. Hippocampus-dependent memory function will be correlated with brain inflammation and aACT levels using behavioural measures of episodic memory in rodents to investigate the relationship between age, diet, inflammation and cognition.