ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Parkinson’s Disease and Aging-related Movement Disorders
Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1608631
This article is part of the Research TopicInterplay between Tau Pathology and Neuroinflammation in Dementia: Bridging Basic and Clinical ScienceView all articles
Increased tau-induced inflammatory responses are associated with a greater degree of atherosclerosis in progressive supranuclear palsy
Provisionally accepted
- 1First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
- 2Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
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A high prevalence of cerebrovascular disease (CVD) has been reported in patients with progressive supranuclear palsy (PSP). However, there is a lack of studies investigating the overlap between PSP and atherosclerotic disease. To address this gap, we conducted a cross-sectional study in a cohort of 56 patients with PSP and 56 healthy controls. Our investigation revealed that patients with PSP had higher maximum carotid plaque thickness (max-CPT), total carotid plaque number (TPN), carotid plaque score (CPS), percentage of maximum carotid stenosis (carotid stenosis%), and magnetic resonance angiography global stenosis score (MRA GSS) than controls, suggesting that patients with PSP have a higher atherosclerotic burden. Further exploration of the underlying mechanism revealed that patients with PSP had elevated levels of total tau, p-tau181, and pro-atherosclerotic inflammatory factors, as well as increased macrophage proportions. Notably, elevated interleukin-6 (IL-6) levels were positively correlated with the degree of atherosclerosis and total tau levels in PSP patients. Finally, we established a mouse model involving the periodic tail vein injection of tau-preformed fibrils (tau-PFFs), which showed localized thickening of the aortic wall, an increased proportion of peripheral blood macrophages, and an enhanced inflammatory response in the plasma and aorta of the mice 3 months after the start of injection. In conclusion, Our study suggested that the tau-induced elevation of plasma inflammatory cytokine levels and macrophage activation are involved in the development of atherosclerosis in patients with PSP. These findings highlight the potential utility of monitoring tau levels and inflammatory markers as biomarkers for assessing atherosclerotic risk in patients with PSP. Furthermore, targeting tau-induced inflammation may represent a novel therapeutic strategy for preventing or managing atherosclerosis in this patient population.
Keywords: Progressive Supranuclear Palsy, Atherosclerosis, Inflammation, tau, macrophage
Received: 09 Apr 2025; Accepted: 18 Jul 2025.
Copyright: © 2025 He, Zhang, Xie, Ji, Deng and Teng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Wen-Jing Deng, First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China
Jun-Fang Teng, First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China
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