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, Hennariikka Koivisto, Jonathan Ray, Meike Hedwig Keuters, Ibrahim Sultan, Flavia Scoyni, Davide Trevisan, Sara Wojciechowski, Mika Kaakinen, Lenka Dvořáková, Abhishek Singh, Jari JukkolaNea Korvenlaita, Lauri Eklund, Jari Koistinaho, Sinem Karaman, Tarja Malm, Heikki Tanila, Kari Alitalo

Research output: Contribution to journalArticleScientificpeer-review

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.

Original languageEnglish
JournalNature Cardiovascular Research
Volume3
Pages (from-to)474–491
Number of pages41
ISSN2731-0590
DOIs
Publication statusPublished - 2024
MoE publication typeA1 Journal article-refereed

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

Fields of Science

  • 3121 General medicine, internal medicine and other clinical medicine

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