The effect of systemic bacterial infection on the onset and progression of disease in an animal model of Alzheimers's disease. (360G-Wellcome-202255_Z_16_Z)

Tg2576 mice will be used as a model of human Alzheimer’s disease (AD). These transgenic mice are genetically modified to overexpress a mutant form of the amyloid precursor protein (APP). APP develops into beta amyloid protein which is a major component of plaques that form in the brain of AD patients. Brain tissue has already been collected at 12, 16 or 20 months. At each stage of the disease mice have been treated with saline or an attenuated strain of Salmonella typhimurium to investigate the hypothesis that systemic bacterial infections modifies plaque formation through promoting neuroinflammation. The ability of microglia and macrophages to phagocytose and proliferate will be investigated. This will help establish if the innate immune response to the infection is causing the increasing amyloid plaque deposition and neuronal loss that causes the onset and/or progression of AD. Antibodies will be used to stain microglial cells (via binding to MHCII, FcRI and CD11b).The antibodies iNOS and Ki67 will be used to analyse the microglia’s ability to perform phagocytosis and proliferating respectively. As well as this, antibodies SMI-32 and NeuN will be used to establish whether damage or swelling has occurred to neurons as a result of the pathogen.