Immunotherapy against amyloid beta is modulated by meningeal lymphatic function VI

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-Aß immunotherapy. Overall design: Brain cells were isolated from 4 months old male 5xFAD mice, after intracisterna magna injections of 5 uL of Visudyne (Vis., verteporfin for injection) alone, or followed by 5 steps of transcranial photoconversion (Vis./photo.), in combination with a series of weekly 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.