{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:05:18Z","timestamp":1789599918386,"version":"build-2803163510"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>It has been reported that progressive supranuclear palsy (PSP) has a higher prevalence of cerebrovascular disease (CVD); however, the relationship between PSP and atherosclerotic disease remains poorly understood. This study aimed to evaluate the burden of atherosclerosis in patients with PSP and explore the potential role of tau-induced inflammation in its pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a cross-sectional study involving 56 patients with PSP and 56 age- and sex-matched healthy controls. Carotid and cerebral atherosclerosis was assessed using ultrasound and magnetic resonance angiography, including measurements of maximum carotid intima-media thickness (max-CIMT), maximum carotid plaque thickness (max-CPT), total plaque number (TPN), carotid plaque score (CPS), maximum carotid stenosis percentage, and global stenosis score (GSS). Plasma levels of traditional atherosclerosis risk factors, total tau, phosphorylated tau (p-tau181, p-tau396), inflammatory cytokines and macrophage proportions were measured. To further investigate the mechanism, we established a mouse model using repeated tail vein injections of tau-preformed fibrils (tau-PFFs), followed by histological and biochemical analysis after 3 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to controls, patients with PSP exhibited significantly higher atherosclerotic burden across most measured vascular parameters. Plasma levels of total tau, p-tau181, macrophage proportions and pro-atherogenic inflammatory markers were elevated in patients with PSP. Among them, elevated interleukin-6 (IL-6) levels were positively correlated with the atherosclerosis severity and total tau levels in patients with PSP. In the tau-PFFs mouse model, localized thickening of the aortic wall, increased circulating macrophages, and enhanced inflammatory responses in both plasma and vascular tissues were observed at 3 months post-injection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings suggest that patients with PSP reveals increased atherosclerotic burden, potentially mediated by tau-induced systemic inflammation and macrophage activation. Monitoring tau levels and inflammatory markers may serve as a valuable approach for assessing vascular risk in patients with PSP. Furthermore, targeting tau-related inflammatory pathways may offer a novel therapeutic strategy for mitigating atherosclerosis in this population.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2025.1608631","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T05:24:15Z","timestamp":1754889855000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Increased tau-induced inflammatory responses are associated with a greater degree of atherosclerosis in progressive supranuclear palsy"],"prefix":"10.3389","volume":"17","author":[{"given":"Yi-Xin","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Fan","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Jing","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Fang","family":"Teng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1038\/s41419-024-07166-8","article-title":"Inflammation in atherosclerosis: Pathophysiology and mechanisms.","volume":"15","author":"Ajoolabady","year":"2024","journal-title":"Cell Death Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.4103\/NRR.NRR-D-23-01770","article-title":"Role of metabolic dysfunction and inflammation along the liver-brain axis in animal models with obesity-induced neurodegeneration.","volume":"20","author":"Asimakidou","year":"2025","journal-title":"Neural Regen. 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