Sustained meningeal lymphatic vessel atrophy or expansion does not alter Alzheimer’s disease-related amyloid pathology
Antila, Salli; Chilov, Dmitri; Nurmi, Harri; Li, Zhilin; Näsi, Anni; Gotkiewicz, Maria; Sitnikova, Valeriia; Jäntti, Henna; Acosta, Natalia; Koivisto, Hennariikka; Ray, Jonathan; Keuters, Meike Hedwig; Sultan, Ibrahim; Scoyni, Flavia; Trevisan, Davide; Wojciechowski, Sara; Kaakinen, Mika; Dvořáková, Lenka; Singh, Abhishek; Jukkola, Jari; Korvenlaita, Nea; Eklund, Lauri; Koistinaho, Jari; Karaman, Sinem; Malm, Tarja; Tanila, Heikki; Alitalo, Kari (2024-03-15)
Antila, Salli
Chilov, Dmitri
Nurmi, Harri
Li, Zhilin
Näsi, Anni
Gotkiewicz, Maria
Sitnikova, Valeriia
Jäntti, Henna
Acosta, Natalia
Koivisto, Hennariikka
Ray, Jonathan
Keuters, Meike Hedwig
Sultan, Ibrahim
Scoyni, Flavia
Trevisan, Davide
Wojciechowski, Sara
Kaakinen, Mika
Dvořáková, Lenka
Singh, Abhishek
Jukkola, Jari
Korvenlaita, Nea
Eklund, Lauri
Koistinaho, Jari
Karaman, Sinem
Malm, Tarja
Tanila, Heikki
Alitalo, Kari
Springer
15.03.2024
Antila, S., Chilov, D., Nurmi, H. et al. Sustained meningeal lymphatic vessel atrophy or expansion does not alter Alzheimer’s disease-related amyloid pathology. Nat Cardiovasc Res 3, 474–491 (2024). https://doi.org/10.1038/s44161-024-00445-9
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© The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
https://creativecommons.org/licenses/by/4.0/
© The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
https://creativecommons.org/licenses/by/4.0/
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202405033102
https://urn.fi/URN:NBN:fi:oulu-202405033102
Tiivistelmä
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.
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.
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