Sustained meningeal lymphatic vessel atrophy or expansion does not alter Alzheimer’s disease-related amyloid pathology
Salli Antila, Dmitri Chilov, Harri Nurmi, Zhilin Li, Anni Näsi, Maria Gotkiewicz, Valeriia Sitnikova, Henna Jäntti, Natalia Acosta‐Baena, Hennariikka Koivisto, J. Ray, Meike Hedwig Keuters, Ibrahim Sultan, Flavia Scoyni, Davide M Trevisan, Sara Wojciechowski, Mika Kaakinen, Lenka Dvořáková, Abhishek Singh, Jari Jukkola, Nea Korvenlaita, Lauri Eklund, Jari Koıstınaho, Sinem Karaman, Tarja Malm, Heikki Tanila, Kari Alitalo
Abstract
Discovery of meningeal lymphatic vessels (LVs) in the dura mater, also known as dural LVs (dLVs) that depend on vascular endothelial growth factor C expression, has raised interest in their possible involvement in Alzheimer's disease (AD). Here we find that in the APdE9 and 5xFAD mouse models of AD, dural amyloid-β (Aβ) is confined to blood vessels and dLV morphology or function is not altered. The induction of sustained dLV atrophy or hyperplasia in the AD mice by blocking or overexpressing vascular endothelial growth factor C, impaired or improved, respectively, macromolecular cerebrospinal fluid (CSF) drainage to cervical lymph nodes. Yet, sustained manipulation of dLVs did not significantly alter the overall brain Aβ plaque load. Moreover, dLV atrophy did not alter the behavioral phenotypes of the AD mice, but it improved CSF-to-blood drainage. Our results indicate that sustained dLV manipulation does not affect Aβ deposition in the brain and that compensatory mechanisms promote CSF clearance.