According to a recent study, modulation of meningeal lymph function can positively influence the outcome of immunotherapy in Alzheimer’s disease (AD). Passive immunotherapy is showing promise as a therapy for AD, but has produced inconsistent results in clinical trials.
The researchers discovered that removing meningeal lymph vessels worsened results in mice treated with immunotherapy. However, delivery of vascular endothelial growth factor C improved immunotherapy.
Mouse models were developed with amyloid deposition expressing 5 mutations found in familial AD. The researchers injected Visudyne and performed sequential transcranial photoconversion steps to remove meningeal lymph vessels. The remaining process involved tissue collection, imaging, mass cytometry, and RNA sequencing.
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The researchers found “a significant overlap between the gene signature of microglia from mice with impaired meningeal lymph function and the transcription profile of activated microglia from the brain of people with AD,” they explained.
The researchers’ extensive data suggest that “it may be possible to develop strategies to therapeutically treat both microglia and the vasculature of the brain, two important contributions to AD pathophysiology, by modulating the function of the lymphatic system at the borders of the brain will, “they explained.
“These results also underscore the importance of early diagnosis and therapeutic intervention in AD, preferably at a stage when the meningeal lymphatic system is still functional. The advanced stage of the disease (or simply advanced age) at which antibody-based therapies are administered could explain some of its marginal beneficial effects (and possible harmful side effects) that could be due to impaired meningeal lymph function. “
reference
Since Mesquita S., Papadopoulos Z., Dykstra T. et al. Meningeal lymph vessels influence the microglial responses and anti-Aβ immunotherapy. Nature. Published online April 28, 2021. doi: 10.1038 / s41586-021-03489-0
This article originally appeared on Psychiatry Advisor
