目的系统评价血清神经丝轻链蛋白(neurofilament light chain protein,NfL)在神经退行性疾病及不同认知损害程度患者中的变化。方法计算机检索PubMed、Embase、Web of Science、中国知网、万方和中国生物医学文献库数据库,纳入阿尔茨海...目的系统评价血清神经丝轻链蛋白(neurofilament light chain protein,NfL)在神经退行性疾病及不同认知损害程度患者中的变化。方法计算机检索PubMed、Embase、Web of Science、中国知网、万方和中国生物医学文献库数据库,纳入阿尔茨海默病(Alzheimer's disease,AD)、帕金森病(Parkinson's disease,PD)、多系统萎缩(multiple system atrophy,MSA)、进行性核上性麻痹(progressive supranuclear palsy,PSP)患者和健康对照均有血清NfL值的队列或病例对照研究,检索时间为建库至2023年4月30日。使用纽卡斯尔-渥太华量表评价纳入研究的风险偏倚,采用RevMan 5.4软件统计分析暴露组与非暴露组间的血清NfL值差异,合并效应量采用标准均数差(standard mean difference,SMD)及95%可信区间(confidence interval,CI)表示。结果纳入43篇文献,共提取了62项对比研究。对PD、AD、MSA、PSP与各自健康对照组分组比较,四组分别纳入9项、24项、9项、8项研究。PD组[SMD=0.27,95%CI(0.17,0.36)]、AD组[SMD=0.97,95%CI(0.70,1.23)]、MSA组[SMD=1.51,95%CI(0.97,2.05)]、PSP组[SMD=1.54,95%CI(1.14,1.93)]血清NfL水平均高于各自健康对照组。对帕金森病认知正常(PD normal cognitive,PD-NC)与帕金森病痴呆(PD with dementia,PD-D)、阿尔茨海默病轻度认知减退(AD mild cognitive impairment,AD-MCI)与阿尔茨海默病痴呆(AD with dementia,AD-D)分组比较,两对比组分别纳入3项和9项研究,PD-D患者血清NfL水平高于PD-NC患者[SMD=0.92,95%CI(0.63,1.20)],AD-D患者血清NfL水平高于AD-MCI患者[SMD=0.61,95%CI(0.49,0.72)]。结论PD、AD、MSA、PSP患者血清NfL水平较健康人群升高,且认知损害程度越大,血清NfL水平越高,血清NfL可能是神经退行性疾病潜在的外周生物标志物,能够进一步反映认知水平的下降。展开更多
Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective d...Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.展开更多
Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is k...Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°C.We aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large cohort.Plasma samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline project.These samples were stored at-80°C for up to 6 years before being used in this study.Our results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage time.However,the level of total tau showed a negative correlation with sample storage time.Notably,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage time.This was not observed in individuals with cognitive impairment.Consequently,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage time.Therefore,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's disease.Furthermore,in cohort studies,it is important to consider the impact of storage time on the overall results.展开更多
文摘目的探讨阿尔茨海默病患者神经丝轻链蛋白(neurofilament light chain,NfL)与临床特点相关性。方法分析2020年6月—2022年12月宁波市第二医院收治的58例阿尔茨海默病患者的临床资料为研究对象。检测58例阿尔茨海默病患者的神经丝轻链蛋白水平。Simoa法检测阿尔茨海默病患者神经丝轻链蛋白水平,探索神经丝轻链蛋白表达与临床因素的关联性。结果58例患者中女性患者33例,NfL水平为(24.93±17.07)pg/ml;男性患者24例,NfL水平为(28.14±17.98)pg/ml,差异无统计学意义。不同文化程度与NfL水平分别为:文盲[(27.87±14.75)pg/ml(7/58)]、小学[(15.22±9.62)pg/ml(7/58)]、初中[(27.95±15.60)pg/ml(14/58)]、高中[(12.84±2.97)pg/ml(4/58)]、中专[(37.35±26.63)pg/ml(7/58)]、大专[(33.79±21.81)pg/ml(5/58)]、大学[(15.22±9.62)pg/ml(7/58)],结果无统计学差异。用相关分析研究NfL和年龄、病程、海马分级,日常生活活动能力评定量表(Activities of Daily Living,ADL)分值,简易精神状态检查表(Mini-Mental State Examination,MMSE)分值,长谷川痴呆量表(Hasegawa Dementia Scale,HDS)分值之间的相关关系,Pearson相关系数(r)表示相关关系的强弱情况。NfL和年龄的r值为0.448,提示NfL和年龄呈正相关。NfL和病程之间的r值为0.045,且P>0.05,说明NfL和病程无相关关系。NfL和海马分级的r值为0.345,说明NfL和海马分级有正相关关系。NfL和ADL分值之间的r值为0.242,P>0.05,说明NfL和ADL分值无相关关系。NfL和MMSE分值的相r值为‒0.099,P>0.05,说明NfL和MMSE分值无相关关系。NfL和HDS分值的r值为‒0.096,P值为0.475>0.05,说明NfL和HDS分值之间没有相关关系。结论阿尔茨海默病患者血清神经丝轻链蛋白水平与患者年龄,磁共振海马分级呈正相关,与性别、文化程度、病程、ADL分值、MMSE分值、HDS分值无相关关系。
文摘目的系统评价血清神经丝轻链蛋白(neurofilament light chain protein,NfL)在神经退行性疾病及不同认知损害程度患者中的变化。方法计算机检索PubMed、Embase、Web of Science、中国知网、万方和中国生物医学文献库数据库,纳入阿尔茨海默病(Alzheimer's disease,AD)、帕金森病(Parkinson's disease,PD)、多系统萎缩(multiple system atrophy,MSA)、进行性核上性麻痹(progressive supranuclear palsy,PSP)患者和健康对照均有血清NfL值的队列或病例对照研究,检索时间为建库至2023年4月30日。使用纽卡斯尔-渥太华量表评价纳入研究的风险偏倚,采用RevMan 5.4软件统计分析暴露组与非暴露组间的血清NfL值差异,合并效应量采用标准均数差(standard mean difference,SMD)及95%可信区间(confidence interval,CI)表示。结果纳入43篇文献,共提取了62项对比研究。对PD、AD、MSA、PSP与各自健康对照组分组比较,四组分别纳入9项、24项、9项、8项研究。PD组[SMD=0.27,95%CI(0.17,0.36)]、AD组[SMD=0.97,95%CI(0.70,1.23)]、MSA组[SMD=1.51,95%CI(0.97,2.05)]、PSP组[SMD=1.54,95%CI(1.14,1.93)]血清NfL水平均高于各自健康对照组。对帕金森病认知正常(PD normal cognitive,PD-NC)与帕金森病痴呆(PD with dementia,PD-D)、阿尔茨海默病轻度认知减退(AD mild cognitive impairment,AD-MCI)与阿尔茨海默病痴呆(AD with dementia,AD-D)分组比较,两对比组分别纳入3项和9项研究,PD-D患者血清NfL水平高于PD-NC患者[SMD=0.92,95%CI(0.63,1.20)],AD-D患者血清NfL水平高于AD-MCI患者[SMD=0.61,95%CI(0.49,0.72)]。结论PD、AD、MSA、PSP患者血清NfL水平较健康人群升高,且认知损害程度越大,血清NfL水平越高,血清NfL可能是神经退行性疾病潜在的外周生物标志物,能够进一步反映认知水平的下降。
文摘Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.
基金supported by the National Key Research&Development Program of China,Nos.2021YFC2501205(to YC),2022YFC24069004(to JL)the STI2030-Major Project,Nos.2021ZD0201101(to YC),2022ZD0211800(to YH)+2 种基金the National Natural Science Foundation of China(Major International Joint Research Project),No.82020108013(to YH)the Sino-German Center for Research Promotion,No.M-0759(to YH)a grant from Beijing Municipal Science&Technology Commission(Beijing Brain Initiative),No.Z201100005520018(to JL)。
文摘Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°C.We aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large cohort.Plasma samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline project.These samples were stored at-80°C for up to 6 years before being used in this study.Our results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage time.However,the level of total tau showed a negative correlation with sample storage time.Notably,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage time.This was not observed in individuals with cognitive impairment.Consequently,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage time.Therefore,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's disease.Furthermore,in cohort studies,it is important to consider the impact of storage time on the overall results.
