Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. Recent research suggests that AD is a neuroinflammatory disease in which the complement system plays a key role. Additionally, there is increasing evidence that extracellular vesicles (EVs) are important mediators in AD pathology. In my project, I aim to study the role of the complement pathway and EVs at the blood-cerebrospinal fluid (CSF) interface, located at the choroid plexus (CP), in AD. Therefore, I will make use of two in vivo mouse models of AD, namely the intracerebroventricular injection of amyloid beta oligomers (AβO) and APP-NLGF knock in mice. Additionally, I will make use of in vitro primary and immortalized mouse CP epithelial (CPE) cells stimulated with AβO and ex vivo CP explants isolated from the different in vivo mouse models or ex vivo stimulated with AβO. In these models, I will study the CP secretome focusing on EVs and complement proteins. Additionally, I aim to identify the recipient cells of CPE-derived EVs by making use of cutting-edge EV labelling and imaging techniques. Furthermore, I will examine the impact of CPE-specific EV blockage and complement deficiency on brain inflammation and AD pathology. In conclusion, this study will without any doubt result in novel knowledge about the role of EVs and the complement pathway at the blood-CSF interface in AD and will form the basis of new innovative future research.