Immunotherapy against amyloid beta is modulated by meningeal lymphatic function II

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: At the age of 4 months, male 5xFAD mice were subjected to an intracisterna magna injection of Visudyne (5 uL) alone (control), or injection of Visudyne (5 uL) followed by 5 steps of transcranial photoconversion using a 689-nm-wavelength non-thermal red light (to induce meningeal lymphatic vessel ablation). Injections were repeated 3 weeks later and mice were euthanized 3 weeks after the last injection. Microglia from the brain cortex were sorted by FACS based on the following phenotype: Singlets SYTOX-Ly6G-CD45+CD11b+. Each individual sample results from brain cortical cells pooled from 3 mice.