Glypican-4 serum levels are associated with cognitive dysfunction and vascular risk factors in Parkinson’s disease
Abstract Glypicans are biomarkers for various pathologies, including cardiovascular disease, cancer and diabetes. Increasing evidence suggests that glypicans also play a role in the context of neurodegenerative disorders. Initially described as supporting functionality of synapses via glutamate rece...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-54800-8 |
| _version_ | 1797274599711309824 |
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| author | Lars Tatenhorst Fabian Maass Hannah Paul Vivian Dambeck Mathias Bähr Rosanna Dono Paul Lingor |
| author_facet | Lars Tatenhorst Fabian Maass Hannah Paul Vivian Dambeck Mathias Bähr Rosanna Dono Paul Lingor |
| author_sort | Lars Tatenhorst |
| collection | DOAJ |
| description | Abstract Glypicans are biomarkers for various pathologies, including cardiovascular disease, cancer and diabetes. Increasing evidence suggests that glypicans also play a role in the context of neurodegenerative disorders. Initially described as supporting functionality of synapses via glutamate receptors during CNS development, Glypican 4 (GPC-4) also plays a role in the context of dementia via tau hyperphosphorylation in Alzheimer’s disease, which is also a co-pathology in Parkinson’s disease dementia. However, clinical evidence of circulating GPC-4 in Parkinson’s disease (PD) is missing so far. We therefore investigated GPC-4 in biofluids of PD patients. We analyzed GPC-4 levels in cerebrospinal fluid (CSF, n = 140), serum (n = 80), and tear fluid samples (n = 70) of PD patients and control subjects in a similar age range by ELISA (serum, CSF) and western blot (tear fluid). Expression of circulating GPC-4 was confirmed in all three biofluids, with highest levels in serum. Interestingly, GPC-4 levels were age-dependent, and multiple regression analysis revealed a significant association between GPC-4 serum levels and MoCA score, suggesting an involvement of GPC-4 in PD-associated cognitive decline. Furthermore, stratification of PD patients for vascular risk factors revealed a significant increase of GPC-4 serum levels in PD patients with vascular risk factors. Our results suggest GPC-4 as a clinical biomarker for vascular risk stratification in order to identify PD patients with increased risk of developing dementia. |
| first_indexed | 2024-03-07T15:01:36Z |
| format | Article |
| id | doaj.art-a8954727db2f4ec38e07fd7bba1622d8 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:01:36Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-a8954727db2f4ec38e07fd7bba1622d82024-03-05T19:09:11ZengNature PortfolioScientific Reports2045-23222024-02-011411710.1038/s41598-024-54800-8Glypican-4 serum levels are associated with cognitive dysfunction and vascular risk factors in Parkinson’s diseaseLars Tatenhorst0Fabian Maass1Hannah Paul2Vivian Dambeck3Mathias Bähr4Rosanna Dono5Paul Lingor6Department of Neurology, University Medical Center GöttingenDepartment of Neurology, University Medical Center GöttingenDepartment of Neurology, University Medical Center GöttingenDepartment of Neurology, University Medical Center GöttingenDepartment of Neurology, University Medical Center GöttingenAix Marseille Univ, CNRS, IBDM, Turing Center for Living Systems, NeuroMarseilleDepartment of Neurology, University Medical Center GöttingenAbstract Glypicans are biomarkers for various pathologies, including cardiovascular disease, cancer and diabetes. Increasing evidence suggests that glypicans also play a role in the context of neurodegenerative disorders. Initially described as supporting functionality of synapses via glutamate receptors during CNS development, Glypican 4 (GPC-4) also plays a role in the context of dementia via tau hyperphosphorylation in Alzheimer’s disease, which is also a co-pathology in Parkinson’s disease dementia. However, clinical evidence of circulating GPC-4 in Parkinson’s disease (PD) is missing so far. We therefore investigated GPC-4 in biofluids of PD patients. We analyzed GPC-4 levels in cerebrospinal fluid (CSF, n = 140), serum (n = 80), and tear fluid samples (n = 70) of PD patients and control subjects in a similar age range by ELISA (serum, CSF) and western blot (tear fluid). Expression of circulating GPC-4 was confirmed in all three biofluids, with highest levels in serum. Interestingly, GPC-4 levels were age-dependent, and multiple regression analysis revealed a significant association between GPC-4 serum levels and MoCA score, suggesting an involvement of GPC-4 in PD-associated cognitive decline. Furthermore, stratification of PD patients for vascular risk factors revealed a significant increase of GPC-4 serum levels in PD patients with vascular risk factors. Our results suggest GPC-4 as a clinical biomarker for vascular risk stratification in order to identify PD patients with increased risk of developing dementia.https://doi.org/10.1038/s41598-024-54800-8Glypican-4BiomarkerParkinson’s diseaseDementiaVascular risk factors |
| spellingShingle | Lars Tatenhorst Fabian Maass Hannah Paul Vivian Dambeck Mathias Bähr Rosanna Dono Paul Lingor Glypican-4 serum levels are associated with cognitive dysfunction and vascular risk factors in Parkinson’s disease Scientific Reports Glypican-4 Biomarker Parkinson’s disease Dementia Vascular risk factors |
| title | Glypican-4 serum levels are associated with cognitive dysfunction and vascular risk factors in Parkinson’s disease |
| title_full | Glypican-4 serum levels are associated with cognitive dysfunction and vascular risk factors in Parkinson’s disease |
| title_fullStr | Glypican-4 serum levels are associated with cognitive dysfunction and vascular risk factors in Parkinson’s disease |
| title_full_unstemmed | Glypican-4 serum levels are associated with cognitive dysfunction and vascular risk factors in Parkinson’s disease |
| title_short | Glypican-4 serum levels are associated with cognitive dysfunction and vascular risk factors in Parkinson’s disease |
| title_sort | glypican 4 serum levels are associated with cognitive dysfunction and vascular risk factors in parkinson s disease |
| topic | Glypican-4 Biomarker Parkinson’s disease Dementia Vascular risk factors |
| url | https://doi.org/10.1038/s41598-024-54800-8 |
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