Tau-mediated Neurodegeneration and Potential Implications in Diagnosis and Treatment of Alzheimer＇s Disease  

作　　者：Xi-Lin Wu Juan Pina-Crespo Yun-Wu Zhang Xiao-Chun Chen Hua-Xi Xu 

机构地区：[1]Neuroscience Initiative, Neuroscience and Aging Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA [2]Department of Neurology, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China [3]Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen University, Xiamen,Fujian 361102, China

出　　处：《Chinese Medical Journal》2017年第24期2978-2990,共13页中华医学杂志（英文版）

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）.

摘　　要：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.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.

关 键 词：Alzheimer＇s Disease BIOMARKER lmmunotherapy Tau Imaging Tau Protein Transcellular Propagation 

分 类 号：R0[医药卫生]