The pathology of Alzheimer’s disease (AD) is complex and involves incompletely understood inflammatory responses. The contributions of inflammatory cells, either resident in the brain (microglia) or recruited from peripheral sources (monocytes/macrophages), are an emerging interest with regard to the initiation and progression of AD. The choroid plexus (CP), which comprises an important part of the interface between the peripheral blood and the cerebrospinal fluid, functions as an immune gateway in the brain and has been proposed to regulate trafficking, activation, and differentiation of inflammatory cells. In a mouse model for aggressive familial AD, we observed upregulated expression of ligands for Siglec-F on CP epithelial cells. Siglec-F, like other members of the Siglec family, binds sialylated glycans to modulate innate and adaptive immune responses in many inflammatory contexts. To explore the role of Siglec ligand expression in normal human CP and in human neurodegenerative disease progression, we have undertaken targeted glycomic and glycoproteomic analysis of Siglec-F and Siglec-9 counterreceptors expressed by choroid plexus papilloma cells (HIBCPP) as well as by 3-D choroid plexus tissue derived from patient induced pluripotent stem cells (choroid plexus organoids, which we call chorganoids). Specific endo-glycosidase digestion and orthogonal biochemical analysis indicates that human CP cells present keratan sulfate ligands for Siglec-9, as well as structurally related ligands for Siglec-F, on polypeptide backbones including low-density lipoprotein receptor-related protein 1 (LRP1) and galectin-3 binding protein/Mac-2 binding protein/90k tumor associated antigen (Gal-3BP). Gal-3BP ligands for Siglec-9 purified from HIBCPP cell media induce inflammatory cell responses using a murine bone marrow derived hematopoietic cell-based screening platform. The identification of these Siglec ligands in a unique tissue setting presents opportunities for investigating the response of inflammatory cells to disease-related glycan expression.