Although well-studied, there are still many questions about the origin of Alzheimer’s disease (AD), making the development of a disease-modifying treatment challenging. Looking at AD from a different angle may boost the design of a more rational approach. Emerging evidence now supports the concept that the immune system plays a key role in AD pathogenesis and leads to the idea that specific parts of the immune system must be fine tuned and engaged to ward off the disease. In this research project, I aim to design an immunomodulatory therapy that stands out from the current therapies as it aims to fine tune and engage the innate and adaptive immune response. I intend to fine tune the innate immune response by using clinical grade extracellular vesicles (WP1). To induce an adaptive immune response, I will use regulatory Chimeric Antigen Receptor (CAR)-T cells against Amyloid-β oligomers (WP2). Finally, in WP3, I evaluate the synergistic effect of a fine tuned innate (WP1) and adaptive (WP2) immune response on AD progression. This conceptually innovative approach will be evaluated in a murine AD model and the results will serve as proof of concept for this new way of approaching the disease. The proposed strategy might not only be applicable in AD but also in other neurodegenerative diseases. Indeed, combining immunomodulatory strategies might tackle the age-related immune exhausted environment more effectively and long-lasting, irrespective of the primary disease etiology.