Programme 9: Characterisation of Aβ and tau strains
Background The two main proteins involved in Alzheimer’s disease, amyloid-β (Aβ) and tau, aggregate in oligomeric and fibrillar forms causing impaired synaptic function, neuroinflammation and neuronal loss, which eventually lead to the full expression of dementia. The precise disease mechanism and the links between these two proteins are still unknown. We are interested in the formation, propagation and spread of Aβ and tau seeds in vivo, and how they influence each other’s pathologies.
Rotation project The project will involve to test the toxicity and aggregation capacity of Aβ and tau seeds from different brain homogenates. We use biosensor cells to quantify tau and Aβ aggregates. The student will learn cell culture techniques, live-imaging, immunostaining and confocal microscopy to characterise the samples. Primary neuronal cultures will be used to determine the toxicity of the seeds.
PhD project The aim of the project is to purify and characterise Aβ and tau seeds present in Alzheimer’s disease brains and mouse models of the disease. Biochemical techniques will be employed to obtain different fractions to be assessed in vitro for toxicity and aggregation by using cell lines and primary cultures. Inoculation of the seeds into Alzheimer’s disease mouse models will provide further confirmation of toxicity and propagation in vivo. Subsequent transmission of the seeds into mice will show if they maintain their specific characteristics and can be classified in strain types.