Elevated Soluble TNF-Receptor 1 in the Serum of Predementia Subjects with Cerebral Small Vessel Disease
Tumor necrosis factor-receptor 1 (TNF-R1)-mediated signaling is critical to the regulation of inflammatory responses. TNF-R1 can be proteolytically released into systemic blood circulation in a soluble form (sTNF-R1), where it binds to circulating TNF and functions to attenuate TNF-mediated inflamma...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/3/525 |
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| author | Kaung H. T. Salai Liu-Yun Wu Joyce R. Chong Yuek Ling Chai Bibek Gyanwali Caroline Robert Saima Hilal Narayanaswamy Venketasubramanian Gavin S. Dawe Christopher P. Chen Mitchell K. P. Lai |
| author_facet | Kaung H. T. Salai Liu-Yun Wu Joyce R. Chong Yuek Ling Chai Bibek Gyanwali Caroline Robert Saima Hilal Narayanaswamy Venketasubramanian Gavin S. Dawe Christopher P. Chen Mitchell K. P. Lai |
| author_sort | Kaung H. T. Salai |
| collection | DOAJ |
| description | Tumor necrosis factor-receptor 1 (TNF-R1)-mediated signaling is critical to the regulation of inflammatory responses. TNF-R1 can be proteolytically released into systemic blood circulation in a soluble form (sTNF-R1), where it binds to circulating TNF and functions to attenuate TNF-mediated inflammation. Increases of peripheral sTNF-R1 have been reported in both Alzheimer’s disease (AD) dementia and vascular dementia (VaD). However, the status of sTNF-R1 in predementia subjects (cognitive impairment, no dementia, CIND) is unknown, and putative associations with cerebral small vessel disease (CSVD), as well as with longitudinal changes in cognitive functions are unclear. We measured baseline serum sTNF-R1 in a longitudinally assessed cohort of 93 controls and 103 CIND, along with neuropsychological evaluations and neuroimaging assessments. Serum sTNF-R1 levels were increased in CIND compared with controls (<i>p</i> < 0.001). Higher baseline sTNF-R1 levels were specifically associated with lacunar infarcts (rate ratio = 6.91, 95% CI 3.19–14.96, <i>p</i> < 0.001), as well as lower rates of cognitive decline in the CIND subgroup. Our data suggest that sTNF-R1 interacts with vascular cognitive impairment in a complex manner at predementia stages, with elevated levels associated with more severe CSVD at baseline, but which may subsequently be protective against cognitive decline. |
| first_indexed | 2024-03-11T06:52:18Z |
| format | Article |
| id | doaj.art-2b962bbbaffa486fa4c0edbaeda7fab6 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T06:52:18Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-2b962bbbaffa486fa4c0edbaeda7fab62023-11-17T09:52:32ZengMDPI AGBiomolecules2218-273X2023-03-0113352510.3390/biom13030525Elevated Soluble TNF-Receptor 1 in the Serum of Predementia Subjects with Cerebral Small Vessel DiseaseKaung H. T. Salai0Liu-Yun Wu1Joyce R. Chong2Yuek Ling Chai3Bibek Gyanwali4Caroline Robert5Saima Hilal6Narayanaswamy Venketasubramanian7Gavin S. Dawe8Christopher P. Chen9Mitchell K. P. Lai10Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, SingaporeDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, SingaporeDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, SingaporeDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, SingaporeDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, SingaporeDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, SingaporeDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, SingaporeRaffles Neuroscience Centre, Raffles Hospital, Singapore 188770, SingaporeDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, SingaporeDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, SingaporeDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, SingaporeTumor necrosis factor-receptor 1 (TNF-R1)-mediated signaling is critical to the regulation of inflammatory responses. TNF-R1 can be proteolytically released into systemic blood circulation in a soluble form (sTNF-R1), where it binds to circulating TNF and functions to attenuate TNF-mediated inflammation. Increases of peripheral sTNF-R1 have been reported in both Alzheimer’s disease (AD) dementia and vascular dementia (VaD). However, the status of sTNF-R1 in predementia subjects (cognitive impairment, no dementia, CIND) is unknown, and putative associations with cerebral small vessel disease (CSVD), as well as with longitudinal changes in cognitive functions are unclear. We measured baseline serum sTNF-R1 in a longitudinally assessed cohort of 93 controls and 103 CIND, along with neuropsychological evaluations and neuroimaging assessments. Serum sTNF-R1 levels were increased in CIND compared with controls (<i>p</i> < 0.001). Higher baseline sTNF-R1 levels were specifically associated with lacunar infarcts (rate ratio = 6.91, 95% CI 3.19–14.96, <i>p</i> < 0.001), as well as lower rates of cognitive decline in the CIND subgroup. Our data suggest that sTNF-R1 interacts with vascular cognitive impairment in a complex manner at predementia stages, with elevated levels associated with more severe CSVD at baseline, but which may subsequently be protective against cognitive decline.https://www.mdpi.com/2218-273X/13/3/525Alzheimer’s diseasebiomarkercerebral small vessel diseasespredementiaserumTNF-receptor 1 |
| spellingShingle | Kaung H. T. Salai Liu-Yun Wu Joyce R. Chong Yuek Ling Chai Bibek Gyanwali Caroline Robert Saima Hilal Narayanaswamy Venketasubramanian Gavin S. Dawe Christopher P. Chen Mitchell K. P. Lai Elevated Soluble TNF-Receptor 1 in the Serum of Predementia Subjects with Cerebral Small Vessel Disease Biomolecules Alzheimer’s disease biomarker cerebral small vessel diseases predementia serum TNF-receptor 1 |
| title | Elevated Soluble TNF-Receptor 1 in the Serum of Predementia Subjects with Cerebral Small Vessel Disease |
| title_full | Elevated Soluble TNF-Receptor 1 in the Serum of Predementia Subjects with Cerebral Small Vessel Disease |
| title_fullStr | Elevated Soluble TNF-Receptor 1 in the Serum of Predementia Subjects with Cerebral Small Vessel Disease |
| title_full_unstemmed | Elevated Soluble TNF-Receptor 1 in the Serum of Predementia Subjects with Cerebral Small Vessel Disease |
| title_short | Elevated Soluble TNF-Receptor 1 in the Serum of Predementia Subjects with Cerebral Small Vessel Disease |
| title_sort | elevated soluble tnf receptor 1 in the serum of predementia subjects with cerebral small vessel disease |
| topic | Alzheimer’s disease biomarker cerebral small vessel diseases predementia serum TNF-receptor 1 |
| url | https://www.mdpi.com/2218-273X/13/3/525 |
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