Immunotherapy against amyloid beta is modulated by meningeal lymphatic function V

A growing body of evidence points to passive immunotherapy as a promising therapeutic strategy against AD. Herein, we show that meningeal lymphatic vasculature becomes dysfunctional in AD transgenic mice and that manipulating meningeal lymphatic drainage affects the outcome of anti-Aβ immunotherapy. Brain cells were isolated from 22-26 months old male APPswe mice, after intracisterna magna injections of 5 uL of AAV1-CMV-eGFP or AAV1-CMV-mVEGF-C (each at 1012 GC/μL) in combination with intraperitoneal injections of mIgG or mAducanumab antibodies (each at 40 mg/kg). Brain cell suspensions were obtained by enzymatic and mechanic digestion of right brain hemisphere tissue, stained for surface markers and enriched for specific populations (microglia/macrophages, blood endothelial cells and mural cells) by FACS sorting. Each individual sample used in this single cell RNA sequencing experiment resulted from brain cells pooled from 3 mice.