Serum Adipsin And Adiponectin In Amyotrophic Lateral Sclerosis

BackgroundAmyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disease involving motoneurons in the cerebral cortex,brainstem and spinal cord,and clinical manifestations of local muscle weakness in insidious onset.Atrophy and pyramidal tract signs,and gradually progress to all skeletal muscle spasms.Typical ALS patients die of respiratory muscle paralysis within 3 to 5 years after onset.Current diagnostics rely primarily on clinical examinations and neuroelectrophysiological examinations,and in most cases,early diagnosis is not possible.Therefore,biomarkers with high sensitivity and specificity are urgently needed to improve the accuracy of early diagnosis of ALS.The pathogenesis of ALS is complex.Neuroinflammation is characterized by microglia activation,astrocyte proliferation and monocyte infiltration,and is involved in the pathogenesis of ALS.In addition,energy metabolism is associated with the course and prognosis of ALS,and a large body of clinical evidence suggests that there is an imbalance in energy homeostasis in ALS patients.Adipokine is a cytokine secreted by adipocytes and acts as a signaling molecule in a variety of signaling pathways.Adipokines(APN)act as hormones to regulate energy balance and neuroinflammatory responses,and participate in the pathogenesis of ALS.Adipsin and adiponectin(APN)are common adipokines.Lipid-lowering protein is involved in the production of complement factor D(CFD),a rate-limiting enzyme in the complement activation pathway,expressed primarily by adipocytes and macrophages.Recent studies have described the new role of the complement system in the pathophysiology of ALS.ObjectiveThis study compared serum APN and CFD levels in ALS patients and control subjects,and assessed their relationship to clinical severity and prognosis to assess whether they could be serum biomarkers for early diagnosis of ALS.Methods55 Clinically diagnosed and probably diagnosed ALS patients were selected according to El Escorial clinical and neurophysiological criteria.At the same time,24 normal subjects with age,gender and case group were selected as the control group.Disease severity was assessed using the ALS Functional Rating Scale Revision(ALSFRS-R)(score range 0-48),and all patients were assessed for cognitive function using the Mini-Mental State Examination(MMSE).After obtaining written informed consent,serum samples from ALS patients and healthy controls were obtained by venous blood sampling,and the concentrations of APN and CFD in serum were determined by ELISA.Statistical analysis software was used to compare the serum concentration of the experimental group and the control group,and the correlation between serum APN and CFD expression levels and clinical symptoms of ALS was analyzed.Multiple linear regression analysis was used to analyze whether APN and CFD were independent of ALS severity.Risk factors,the receiver operating curve(receiver operating characteristic(ROC))was used to evaluate the value of APN and CFD in the diagnosis of ALS.ResultsThe serum CFD level(34.41 ± 13.66 ?g/ml)was significantly higher in the ALS group than in the healthy control group(24.92± 11.30 ug/mL,P<0.01).The expression level of APN in ALS patients was 64.25± 27.16.Mg/ml,higher than the healthy control group expression level 48.21 ± 23.79 ?g/ml,(P<0.05).The expression of APN in the medulla obtus disease was significantly higher than that in the spinal cord(55.52± 27.76 ?g/ml,P = 0.037).The expression of CFD in ALS patients with medullary onset(36.55 ± 15.96 ?g/ml)Higher than ALS patients with spinal cord onset(33.61 ± 12.82 ?g/ml),but not statistically significant(P = 0.483).Patients with medullary onset developed faster than patients with spinal cord onset(P=0.048).Pearson correlation analysis showed that CFD(r =-0.574,P = 0.024)and APN(r=-0.534,P = 0.015)expression levels were negatively correlated with ALSFRS-R score.Multiple linear regression analysis showed that CFD(?=-0.381,P =0.019)and APN(?=-0.399,P =0.015)were independent factors affecting ALSFRS-R.Through the ROC curve,the sensitivity of CFD for ALS diagnosis was 65.5%,the specificity was 70.8%,the area under the curve(AUC)was 0.707,the 95%confidence interval was 0.583-0.831,the P value was<0.001,and the cut-off value was 28.07 ?g/Ml.The sensitivity of APN for the diagnosis of ALS was 72.7%,the specificity was 62.5%,and the area under the curve(AUC)was 0.668,95%confidence interval 0.540-0.769,P value<0.05,and the critical value was 48.41 ?g/ml.Both CFD and APN have significant significance in the diagnosis of ALS.CFD has greater value in diagnosing ALS.Conclusion1.The expression levels of serum CFD and APN in ALS patients are higher than those in healthy people;2.The expression levels of CFD and APN are related to the ALSFRS-R score of ALS patients;3,CFD and APN can be used as biomarkers to assist ALS diagnosis.