Study Of Serum And CSF Biomarkers In ALS Patients

Biomarker has been defined as a characteristic that is objectively measured and evaluated as an indicator of normal biological processes,pathological processes,or biological response to a therapeutic intervention.Which could assist in the early diagnosis,phenotype identification,observation of the therapy efficacy,monitor the disease progression and understanding the potential pathogenesis of the disease.Amyotrophic lateral sclerosis(ALS)is a slowly progressive neurodegenerative disease.The diagnosis of ALS is mainly based detailed neurological examination,precise neuroelectrophysiological examination and exclude other diseases with similar clinical manifestations.There are no effective biomarkers for early diagnosis,phenotype identification and prognosis evaluation.At present,biomarkers have been extensively explored in the fields of genes,inflammation,oxidative stress and metabolism.However,there are still no reliable biomarkers for guiding clinical applications.Recent studies have shown that NFs,tau and Cys C present in the pathology of ALS.They could result in the death of motor neuron with the change of pathological marker in CSF,which might become the biomarker of ALS.However,blood biomarker is usually the simplest,convenient and direct method to assist in diagnosis and prognosis evaluation of disease.Preliminary studies have indicated that there are abnormalities of NFs,tau and Cys C in the CSF and serum of ALS patients,but there are no consensus in this field.In this study,we measured NF-L,NF-M,NF-H,t-tau,p-tau,t-tau and Cys C proteins in CSF and serum by ELISA and Cys C in serum by latex particle enhanced immunoturbidimetry.Then we analysis the correlation between them and disease course,disease severity,disease progression,prognosis and cognition to clarify their role in the early diagnosis,phenotype identification,disease progression and prognosis evaluation.In the first part of the study,we demonstrate that CSF and serum NF-L levels increased in patients with ALS,while serum and CSF NF-H and NF-M levels were not significantly different from those in the control group;CSF and serum NF-L levels were negatively correlated with the ALSFRS-r score,were positively correlated with the decrease of the ALSFRS-r score,DPR,and UMN score,and were not linearly correlated with duration.CSF NF-L level and serum NF-L level are positive correlated.Further analysis find that CSF and serum NF-L level in slow progression group and rapid progression group are higher than in control group.In slow progression group,serum NF-L level are positive correlated with DPR.In rapid progression group,CSF and serum NF-L are positive correlated with DPR.ALS patients with lower levels of serum NF-L had higher survival rate than patients with higher levels of NF-L.In addition,ALS patients with lower levels of serum NF-L had longer TTG than patients with higher levels of NF-L.In conclusion,CSF and serum NF-L levels may be a biomarker that could predict the severity,progression and survival of patients with ALS.In the second part of the study,the data indicat that CSF p-tau levels and p-tau/t-tau ratio are reduced in patients with ALS,it has,p-tau/t-tau,higher sensitivity and specificity when compared with OND,might reflect the pathophysiological changes of ALS patients.Increased p-tau in CSF correlated with injury of upper motor neuron,which indicated the impairment of UMN.In addition,we also demonstrated that CSF p-tau was negatively correlated with cognitive impairment in ALS patients with cognition dysfunction,high CSF p-tau may be one of the contributing factors of cognitive impairment in ALS patients.In the third part of the study,Results show that CSF Cys C levels in ALS and AD decreased compared to the OND,CSF Cys C level in ALS was lower than in AM.The serum Cys C levels of ALS in 12^thmonth and 18^thmoth after enrolled were lower than in the baseline.Our data also showed that the serum and CSF Cys C level in ALS patient was positively correlated with Mo CA and ECSA score,and the decrease of Cys C level may be one of the contributing factors of cognitive impairment in ALS.In conclusion,this study indicates that CSF and serum NF-L may be an effective biomarker in ALS,it may be a biomarker that could predict the severity,progression and survival of ALS patients.High p-tau and low Cys C may be recognized as one of the contributing factors in the cognition dysfunction of ALS.