Objective：To review recent research advances on tau,a major player in Alzheimer＇s disease （AD） pathogenesis,a biomarker for AD onset,and potential target for AD therapy.Data Sources：This review was based on a com...Objective：To review recent research advances on tau,a major player in Alzheimer＇s disease （AD） pathogenesis,a biomarker for AD onset,and potential target for AD therapy.Data Sources：This review was based on a comprehensive search using online literature databases,including PubMed,Web of Science,and Google Scholar.Study Selection：Literature search was based on the following keywords：Alzheimer＇s disease,tau protein,biomarker,cerebrospinal fluid （CSF）,therapeutics,plasma,imaging,propagation,spreading,seeding,prion,conformational templating,and posttranslational modification.Relevant articles were carefully reviewed,with no exclusions applied to study design and publication type.Results：Amyloid plaques enriched with extracellular amyloid beta （Aβ） and intracellular neurofibrillary tangles comprised of hyperphosphorylated tau proteins are the two main pathological hallmarks ofAD.Although the Aβ hypothesis has dominated AD research for many years,clinical Aβ-targeting strategies have consistently failed to effectively treat AD or prevent AD onset.The research focus in AD has recently shifted to the role oftau in AD.In addition to phosphorylation,tau is acetylated and proteolytically cleaved,which also contribute to its physiological and pathological functions.Emerging evidence characterizing pathological tau propagation and spreading provides new avenues for research into the molecular and cellular mechanisms underlying AD pathogenesis.Techniques to detect tau at minute levels in CSF and blood have been developed,and improved tracers have facilitated tau imaging in the brain.These advances have potential to accurately determine tau levels at early diagnostic stages in AD.Given that tau is a potential therapeutic target,anti-tau immunotherapy may potentially be a viable treatment strategy in AD intervention.Conclusion：Detecting changes in tau and targeting tau pathology represent a promising lead in the diagnosis and treatment of AD.展开更多
背景部分生物学标志物可用于新生儿缺氧缺血性脑病(HIE)的诊断及其预后评估,但目前血清尿酸、Tau蛋白水平与新生儿HIE患儿神经发育预后的关系尚未明确。目的分析中重度新生儿HIE患儿血清尿酸、Tau蛋白水平变化及其与窒息程度、神经发育...背景部分生物学标志物可用于新生儿缺氧缺血性脑病(HIE)的诊断及其预后评估,但目前血清尿酸、Tau蛋白水平与新生儿HIE患儿神经发育预后的关系尚未明确。目的分析中重度新生儿HIE患儿血清尿酸、Tau蛋白水平变化及其与窒息程度、神经发育预后的相关性。方法选取2014年8月-2015年8月邯郸市妇幼保健院新生儿重症监护室收治的中重度新生儿HIE患儿41例作为观察组,另选取同期在本院出生的健康足月新生儿35例作为对照组。比较两组新生儿、中重度患儿、不同神经发育预后患儿血清尿酸、Tau蛋白水平及出生5 min Apgar评分;血清尿酸水平与中重度新生儿HIE患儿血清Tau蛋白水平、出生5 min Apgar评分、总发育商的相关性及血清Tau蛋白水平与中重度新生儿HIE患儿出生5 min Apgar评分、总发育商的相关性分析采用Pearson相关分析。结果 (1)观察组患儿血清尿酸、Tau蛋白水平高于对照组,出生5 min Apgar评分低于对照组(P<0.01)。(2)重度患儿血清尿酸、Tau蛋白水平高于中度患儿,出生5 min Apgar评分低于中度患儿(P<0.05)。(3)不同神经发育预后患儿血清尿酸水平比较,差异无统计学意义(P>0.05);边缘状态和发育迟缓患儿血清Tau蛋白水平高于发育良好患儿,发育迟缓患儿出生5 min Apgar评分低于发育良好患儿(P<0.05)。(4)Pearson相关分析结果显示,血清尿酸水平与中重度新生儿HIE患儿血清Tau蛋白水平(r=0.299,P=0.097)、总发育商(r=-0.203,P=0.256)无直线相关关系,但与出生5 min Apgar评分呈负相关(r=-0.729,P<0.01);血清Tau水平与中重度新生儿HIE患儿出生5 min Apgar评分(r=-0.370,P=0.017)、总发育商(r=-0.617,P<0.01)呈负相关。结论中重度新生儿HIE患儿出生后24 h内血清尿酸、Tau蛋白水平明显升高,二者均与患儿出生时窒息程度有关;血清Tau蛋白水平与患儿神经发育预后呈负相关,而血清尿酸水平与患儿神经发育预后无直线展开更多
基金This work was supported by grants from the National Natural Science Foundation of China （No. 81671352, 91232709）, the National Key Project of Research and Development Plan （No. 2016YFC1306404）, the National Institute of Health （No. R21 AG048519, R01 AG021173, R01 AG038710, R01 AG044420, R01 NS046673, RF1 AG056130, and RF1 AG056114）, the Tanz Family Fund as well as scholarship from China Scholarship Council （No. 201608350068）.
文摘Objective：To review recent research advances on tau,a major player in Alzheimer＇s disease （AD） pathogenesis,a biomarker for AD onset,and potential target for AD therapy.Data Sources：This review was based on a comprehensive search using online literature databases,including PubMed,Web of Science,and Google Scholar.Study Selection：Literature search was based on the following keywords：Alzheimer＇s disease,tau protein,biomarker,cerebrospinal fluid （CSF）,therapeutics,plasma,imaging,propagation,spreading,seeding,prion,conformational templating,and posttranslational modification.Relevant articles were carefully reviewed,with no exclusions applied to study design and publication type.Results：Amyloid plaques enriched with extracellular amyloid beta （Aβ） and intracellular neurofibrillary tangles comprised of hyperphosphorylated tau proteins are the two main pathological hallmarks ofAD.Although the Aβ hypothesis has dominated AD research for many years,clinical Aβ-targeting strategies have consistently failed to effectively treat AD or prevent AD onset.The research focus in AD has recently shifted to the role oftau in AD.In addition to phosphorylation,tau is acetylated and proteolytically cleaved,which also contribute to its physiological and pathological functions.Emerging evidence characterizing pathological tau propagation and spreading provides new avenues for research into the molecular and cellular mechanisms underlying AD pathogenesis.Techniques to detect tau at minute levels in CSF and blood have been developed,and improved tracers have facilitated tau imaging in the brain.These advances have potential to accurately determine tau levels at early diagnostic stages in AD.Given that tau is a potential therapeutic target,anti-tau immunotherapy may potentially be a viable treatment strategy in AD intervention.Conclusion：Detecting changes in tau and targeting tau pathology represent a promising lead in the diagnosis and treatment of AD.
文摘背景部分生物学标志物可用于新生儿缺氧缺血性脑病(HIE)的诊断及其预后评估,但目前血清尿酸、Tau蛋白水平与新生儿HIE患儿神经发育预后的关系尚未明确。目的分析中重度新生儿HIE患儿血清尿酸、Tau蛋白水平变化及其与窒息程度、神经发育预后的相关性。方法选取2014年8月-2015年8月邯郸市妇幼保健院新生儿重症监护室收治的中重度新生儿HIE患儿41例作为观察组,另选取同期在本院出生的健康足月新生儿35例作为对照组。比较两组新生儿、中重度患儿、不同神经发育预后患儿血清尿酸、Tau蛋白水平及出生5 min Apgar评分;血清尿酸水平与中重度新生儿HIE患儿血清Tau蛋白水平、出生5 min Apgar评分、总发育商的相关性及血清Tau蛋白水平与中重度新生儿HIE患儿出生5 min Apgar评分、总发育商的相关性分析采用Pearson相关分析。结果 (1)观察组患儿血清尿酸、Tau蛋白水平高于对照组,出生5 min Apgar评分低于对照组(P<0.01)。(2)重度患儿血清尿酸、Tau蛋白水平高于中度患儿,出生5 min Apgar评分低于中度患儿(P<0.05)。(3)不同神经发育预后患儿血清尿酸水平比较,差异无统计学意义(P>0.05);边缘状态和发育迟缓患儿血清Tau蛋白水平高于发育良好患儿,发育迟缓患儿出生5 min Apgar评分低于发育良好患儿(P<0.05)。(4)Pearson相关分析结果显示,血清尿酸水平与中重度新生儿HIE患儿血清Tau蛋白水平(r=0.299,P=0.097)、总发育商(r=-0.203,P=0.256)无直线相关关系,但与出生5 min Apgar评分呈负相关(r=-0.729,P<0.01);血清Tau水平与中重度新生儿HIE患儿出生5 min Apgar评分(r=-0.370,P=0.017)、总发育商(r=-0.617,P<0.01)呈负相关。结论中重度新生儿HIE患儿出生后24 h内血清尿酸、Tau蛋白水平明显升高,二者均与患儿出生时窒息程度有关;血清Tau蛋白水平与患儿神经发育预后呈负相关,而血清尿酸水平与患儿神经发育预后无直线
