Brain homeostasis depends on barriers separating blood from the central nervous system (CNS). The choroid plexus is such a barrier and can be found in the four ventricles of the brain and is characterized by a single layer of choroid plexus epithelial (CPE) cells surrounding stroma and leaky capillaries thereby creating the blood-cerebrospinal fluid (CSF) barrier. Additionally, the choroid plexus is involved in CSF production and detoxification, immune surveillance and molecular transport from blood to the CNS. Convincing evidence revealed a central role of the choroid plexus in several brain inflammatory diseases. Nevertheless, the choroid plexus is one of the most understudied brain regions. Moreover, most choroid plexus research is performed on all choroid plexus tissues pooled together and thus results are averaged across them. However, increasing evidence suggests that the lateral (LV) and fourth (4V) choroid plexus have very distinct properties in homeostasis and disease. Here, we will study spatial and cellular heterogeneity of the LV and 4V choroid plexus in healthy adult mice. Next, we will assess the (changes in) presence and diversity of inflammatory cells in both choroid plexuses in mouse models for systemic inflammation and Alzheimer’s disease, together with the cell-type specific expression changes. In conclusion, this project aims to unravel the choroid plexus heterogeneity in health and disease using single cell analysis in different mouse models.