ArticleScientific reports2024
Glypican-4 serum levels are associated with cognitive dysfunction and vascular risk factors in Parkinson's disease.
Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- β-Amyloid induces microglial expression of GPC4 and APOE leading to increased neuronal tau pathology and toxicity.Molecular neurodegeneration · 2025Article
- Large-scale plasma proteomics uncovers preclinical molecular signatures of Parkinson's disease and overlap with other neurodegenerative disorders.medRxiv : the preprint server for health sciences · 2025Article
- The ocular surface tear film as a biomarker for systemic health.The ocular surface · 2025Review
- Evaluation of circulating glypican 4 as a novel biomarker in disease - A comprehensive review.Journal of molecular medicine (Berlin, Germany) · 2025Review
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
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.
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