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

Abstract

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.