Increased tau-induced inflammatory responses are associated with a greater degree of atherosclerosis in progressive supranuclear palsy
IntroductionIt 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 wit...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-08-01
|
| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2025.1608631/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850033517132513280 |
|---|---|
| author | Yi-Xin He Yi-Xin He Rui Zhang Rui Zhang Chen Xie Si-Fan Ji Wen-Jing Deng Wen-Jing Deng Jun-Fang Teng Jun-Fang Teng |
| author_facet | Yi-Xin He Yi-Xin He Rui Zhang Rui Zhang Chen Xie Si-Fan Ji Wen-Jing Deng Wen-Jing Deng Jun-Fang Teng Jun-Fang Teng |
| author_sort | Yi-Xin He |
| collection | DOAJ |
| description | IntroductionIt 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.MethodsWe 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.ResultsCompared 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.ConclusionOur 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. |
| format | Article |
| id | doaj-art-ed8b7f31e6644dd3b75911b45d7f0413 |
| institution | DOAJ |
| issn | 1663-4365 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj-art-ed8b7f31e6644dd3b75911b45d7f04132025-08-20T02:58:11ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652025-08-011710.3389/fnagi.2025.16086311608631Increased tau-induced inflammatory responses are associated with a greater degree of atherosclerosis in progressive supranuclear palsyYi-Xin He0Yi-Xin He1Rui Zhang2Rui Zhang3Chen Xie4Si-Fan Ji5Wen-Jing Deng6Wen-Jing Deng7Jun-Fang Teng8Jun-Fang Teng9Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaHenan Neurological Disease Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaHenan Neurological Disease Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaOffice of Citizen Affair, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaHenan Neurological Disease Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaHenan Neurological Disease Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaIntroductionIt 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.MethodsWe 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.ResultsCompared 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.ConclusionOur 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.https://www.frontiersin.org/articles/10.3389/fnagi.2025.1608631/fullprogressive supranuclear palsyatherosclerosisinflammationtaumacrophage |
| spellingShingle | Yi-Xin He Yi-Xin He Rui Zhang Rui Zhang Chen Xie Si-Fan Ji Wen-Jing Deng Wen-Jing Deng Jun-Fang Teng Jun-Fang Teng Increased tau-induced inflammatory responses are associated with a greater degree of atherosclerosis in progressive supranuclear palsy Frontiers in Aging Neuroscience progressive supranuclear palsy atherosclerosis inflammation tau macrophage |
| title | Increased tau-induced inflammatory responses are associated with a greater degree of atherosclerosis in progressive supranuclear palsy |
| title_full | Increased tau-induced inflammatory responses are associated with a greater degree of atherosclerosis in progressive supranuclear palsy |
| title_fullStr | Increased tau-induced inflammatory responses are associated with a greater degree of atherosclerosis in progressive supranuclear palsy |
| title_full_unstemmed | Increased tau-induced inflammatory responses are associated with a greater degree of atherosclerosis in progressive supranuclear palsy |
| title_short | Increased tau-induced inflammatory responses are associated with a greater degree of atherosclerosis in progressive supranuclear palsy |
| title_sort | increased tau induced inflammatory responses are associated with a greater degree of atherosclerosis in progressive supranuclear palsy |
| topic | progressive supranuclear palsy atherosclerosis inflammation tau macrophage |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2025.1608631/full |
| work_keys_str_mv | AT yixinhe increasedtauinducedinflammatoryresponsesareassociatedwithagreaterdegreeofatherosclerosisinprogressivesupranuclearpalsy AT yixinhe increasedtauinducedinflammatoryresponsesareassociatedwithagreaterdegreeofatherosclerosisinprogressivesupranuclearpalsy AT ruizhang increasedtauinducedinflammatoryresponsesareassociatedwithagreaterdegreeofatherosclerosisinprogressivesupranuclearpalsy AT ruizhang increasedtauinducedinflammatoryresponsesareassociatedwithagreaterdegreeofatherosclerosisinprogressivesupranuclearpalsy AT chenxie increasedtauinducedinflammatoryresponsesareassociatedwithagreaterdegreeofatherosclerosisinprogressivesupranuclearpalsy AT sifanji increasedtauinducedinflammatoryresponsesareassociatedwithagreaterdegreeofatherosclerosisinprogressivesupranuclearpalsy AT wenjingdeng increasedtauinducedinflammatoryresponsesareassociatedwithagreaterdegreeofatherosclerosisinprogressivesupranuclearpalsy AT wenjingdeng increasedtauinducedinflammatoryresponsesareassociatedwithagreaterdegreeofatherosclerosisinprogressivesupranuclearpalsy AT junfangteng increasedtauinducedinflammatoryresponsesareassociatedwithagreaterdegreeofatherosclerosisinprogressivesupranuclearpalsy AT junfangteng increasedtauinducedinflammatoryresponsesareassociatedwithagreaterdegreeofatherosclerosisinprogressivesupranuclearpalsy |