Dysfunctional vascular smooth muscle cells mediate early and late-stage neuroinflammation and Tau hyperphosphorylation
JORGE AGUILAR PINEDA,
Karin Vera lopez,
Gonzalo Davila Del-Carpio,
Clint L Miller,
Mark E. Lindsay,
christian lack lino cardenas
Posted 14 Apr 2021
bioRxiv DOI: 10.1101/2021.04.13.439741
Posted 14 Apr 2021
Despite the emerging evidence implying early vascular contributions to neurogenerative syndromes, the role of vascular smooth muscle cells (VSMCs) in the pathogenesis of Alzheimer disease is still not well understood. Herein, we show that VSMCs in brains of AD patients and the animal model of the disease, are deficient in multiple VSMC-contractile markers which correlated with Tau accumulation in brain arterioles. Ex vivo and in vitro experiments demonstrated that VSMCs undergo dramatic phenotypic transitions under AD-like conditions, adopting pro-inflammatory and synthetic phenotypes. Notably, these changes coincided with Tau hyperphosphorylation at residues Y18, T205 and S262. We also observed that loss of VSMC markers occurred in an age-dependent manner, and that expression of Sm22-a and a-Sma proteins were inversely correlated with CD68 and Tau accumulation in brain arterioles of 3xTg-AD mice. Together, these findings further support the contribution of VSMCs in AD pathogenesis, and nominate VSMCs as potential novel therapeutic target in AD.
- Downloaded 268 times
- Download rankings, all-time:
- Site-wide: 115,796
- In neuroscience: 17,393
- Year to date:
- Site-wide: 31,407
- Since beginning of last month:
- Site-wide: 21,551
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!