Platelet glycogen synthase kinase 3β regulates plasma β amyloid and phosphorylated tau levels in chronic kidney disease patients with cognitive dysfunction; therapeutic role of erythropoietin
Introduction: Patients with chronic kidney disease (CKD) have increasingly been diagnosed with cognitive impairment. Glycogen synthase kinase 3β (GSK3β) is directly causing both phosphorylated tau (pTau) and amyloid β (Aβ) accumulation in Alzheimer’s disease (AD). GSK3β expression is more abundant i...
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| Format: | Article |
| Language: | English |
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Society of Diabetic Nephropathy Prevention
2023-09-01
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| Series: | Journal of Nephropathology |
| Subjects: | |
| Online Access: | https://nephropathol.com/PDF/jnp-12-e17238.pdf |
| _version_ | 1797676471871864832 |
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| author | Vinothkumar Ganesan Krishnakumar Sethuraman Sureshkumar Sureshkumar Venkataraman Prabhu |
| author_facet | Vinothkumar Ganesan Krishnakumar Sethuraman Sureshkumar Sureshkumar Venkataraman Prabhu |
| author_sort | Vinothkumar Ganesan |
| collection | DOAJ |
| description | Introduction: Patients with chronic kidney disease (CKD) have increasingly been diagnosed with cognitive impairment. Glycogen synthase kinase 3β (GSK3β) is directly causing both phosphorylated tau (pTau) and amyloid β (Aβ) accumulation in Alzheimer’s disease (AD). GSK3β expression is more abundant in human platelets than in other blood cells. Recombinant human erythropoietin (rHuEPO) is a common medicine for treating anemia in patients with CKD, as well as a neuroprotective agent. Objectives: The goal of this research is to find out how platelet GSK3β regulates plasma Aβ, total Tau and tau phosphorylated at threonine 181 (p-tau181) levels in CKD patients with cognitive dysfunction and also the efficacy of rHuEPO treatment. Patients and Methods: The study included 60 participants, which consist of 30 CKD without cognitive dysfunction and 30 CKD with cognitive dysfunction based on the neuropsychological examination. The expression of GSK3β in platelets was evaluated using a western blot and plasma Aβ, total Tau, pTau 181 levels were quantified by ELISA. The data were compared statistically (P< 0.05) to AD, normocytic normochromic anemic and healthy patients. Results: In CKD with cognitive dysfunction subjects, platelet GSK3β expression and plasma Aβ, total Tau and pTau181 levels were significantly (P< 0.05) altered like AD when compared to normocytic normochromic anemic, healthy and CKD without cognitive dysfunction subjects. In post rHuEPO (100 IU/kg, weekly twice, six months) treatment, the altered protein abnormalities were retrieved significantly (P<0.05) compared to pre-treatment. Conclusion: This study established that platelet GSK3β expression and plasma Aβ, total Tau, pTau181 are the candidate biomarkers for cognitive dysfunction in CKD patients. The clinical utility of rHuEPO as a GSK3β inhibitor and therapeutic agent for cognitive dysfunction in CKD has been determined. |
| first_indexed | 2024-03-11T22:28:38Z |
| format | Article |
| id | doaj.art-29684b4bc862419eb5a4b846517d77fd |
| institution | Directory Open Access Journal |
| issn | 2251-8363 2251-8819 |
| language | English |
| last_indexed | 2024-03-11T22:28:38Z |
| publishDate | 2023-09-01 |
| publisher | Society of Diabetic Nephropathy Prevention |
| record_format | Article |
| series | Journal of Nephropathology |
| spelling | doaj.art-29684b4bc862419eb5a4b846517d77fd2023-09-23T11:33:13ZengSociety of Diabetic Nephropathy PreventionJournal of Nephropathology2251-83632251-88192023-09-01124e17238e1723810.34172/jnp.2022.17238jnp-17238Platelet glycogen synthase kinase 3β regulates plasma β amyloid and phosphorylated tau levels in chronic kidney disease patients with cognitive dysfunction; therapeutic role of erythropoietinVinothkumar Ganesan0Krishnakumar Sethuraman1Sureshkumar Sureshkumar2Venkataraman Prabhu3Department of Medical Research, SRM Medical college Hospital, SRM Institute of Science and Technology, Chennai, IndiaDepartment of Nephrology, SRM Medical college Hospital, SRM Institute of Science and Technology, Chennai, IndiaDepartment of Neurology, Balaji Medical College Hospital, Chrompet, Chennai, IndiaDepartment of Medical Research, SRM Medical college Hospital, SRM Institute of Science and Technology, Chennai, IndiaIntroduction: Patients with chronic kidney disease (CKD) have increasingly been diagnosed with cognitive impairment. Glycogen synthase kinase 3β (GSK3β) is directly causing both phosphorylated tau (pTau) and amyloid β (Aβ) accumulation in Alzheimer’s disease (AD). GSK3β expression is more abundant in human platelets than in other blood cells. Recombinant human erythropoietin (rHuEPO) is a common medicine for treating anemia in patients with CKD, as well as a neuroprotective agent. Objectives: The goal of this research is to find out how platelet GSK3β regulates plasma Aβ, total Tau and tau phosphorylated at threonine 181 (p-tau181) levels in CKD patients with cognitive dysfunction and also the efficacy of rHuEPO treatment. Patients and Methods: The study included 60 participants, which consist of 30 CKD without cognitive dysfunction and 30 CKD with cognitive dysfunction based on the neuropsychological examination. The expression of GSK3β in platelets was evaluated using a western blot and plasma Aβ, total Tau, pTau 181 levels were quantified by ELISA. The data were compared statistically (P< 0.05) to AD, normocytic normochromic anemic and healthy patients. Results: In CKD with cognitive dysfunction subjects, platelet GSK3β expression and plasma Aβ, total Tau and pTau181 levels were significantly (P< 0.05) altered like AD when compared to normocytic normochromic anemic, healthy and CKD without cognitive dysfunction subjects. In post rHuEPO (100 IU/kg, weekly twice, six months) treatment, the altered protein abnormalities were retrieved significantly (P<0.05) compared to pre-treatment. Conclusion: This study established that platelet GSK3β expression and plasma Aβ, total Tau, pTau181 are the candidate biomarkers for cognitive dysfunction in CKD patients. The clinical utility of rHuEPO as a GSK3β inhibitor and therapeutic agent for cognitive dysfunction in CKD has been determined.https://nephropathol.com/PDF/jnp-12-e17238.pdfchronic kidney diseasecognitive impairmentaβtau proteingsk3βrecombinant human erythropoietin |
| spellingShingle | Vinothkumar Ganesan Krishnakumar Sethuraman Sureshkumar Sureshkumar Venkataraman Prabhu Platelet glycogen synthase kinase 3β regulates plasma β amyloid and phosphorylated tau levels in chronic kidney disease patients with cognitive dysfunction; therapeutic role of erythropoietin Journal of Nephropathology chronic kidney disease cognitive impairment aβ tau protein gsk3β recombinant human erythropoietin |
| title | Platelet glycogen synthase kinase 3β regulates plasma β amyloid and phosphorylated tau levels in chronic kidney disease patients with cognitive dysfunction; therapeutic role of erythropoietin |
| title_full | Platelet glycogen synthase kinase 3β regulates plasma β amyloid and phosphorylated tau levels in chronic kidney disease patients with cognitive dysfunction; therapeutic role of erythropoietin |
| title_fullStr | Platelet glycogen synthase kinase 3β regulates plasma β amyloid and phosphorylated tau levels in chronic kidney disease patients with cognitive dysfunction; therapeutic role of erythropoietin |
| title_full_unstemmed | Platelet glycogen synthase kinase 3β regulates plasma β amyloid and phosphorylated tau levels in chronic kidney disease patients with cognitive dysfunction; therapeutic role of erythropoietin |
| title_short | Platelet glycogen synthase kinase 3β regulates plasma β amyloid and phosphorylated tau levels in chronic kidney disease patients with cognitive dysfunction; therapeutic role of erythropoietin |
| title_sort | platelet glycogen synthase kinase 3β regulates plasma β amyloid and phosphorylated tau levels in chronic kidney disease patients with cognitive dysfunction therapeutic role of erythropoietin |
| topic | chronic kidney disease cognitive impairment aβ tau protein gsk3β recombinant human erythropoietin |
| url | https://nephropathol.com/PDF/jnp-12-e17238.pdf |
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