Many brain diseases show an activation of the immune system and this immune response can contribute to disease severity. The brain’s immune response can be altered by inflammatory events outside of the brain, and our previous work demonstrated that this leads to long-lasting changes in the immune response, which in turn alters the progression of Alzheimer’s disease pathology in animal models. Thus, the brain’s immune cells have an immunological memory function, which can impact on brain diseases that develop much later in life. In this project, we will characterise the underlying molecular mechanisms in detail and analyse them for the first time in tissue from brain donors. This could lead to new approaches for the treatment of neurodegenerative disorders.