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

• Published in: Chinese medical journal Vol. 130; no. 24; pp. 2978 - 2990
• Main Authors: Wu, Xi-Lin, Piña-Crespo, Juan, Zhang, Yun-Wu, Chen, Xiao-Chun, Xu, Hua-Xi
• Format: Journal Article
• Language: English
• Published: China Medknow Publications and Media Pvt. Ltd 20.12.2017; Lippincott Williams & Wilkins Ovid Technologies; 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%Neuroscience Initiative, Neuroscience and Aging Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA%Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen University, Xiamen,Fujian 361102, China%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%Neuroscience Initiative, Neuroscience and Aging Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; Neuroscience Initiative, Neuroscience and Aging Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen University, Xiamen,Fujian 361102, China; Medknow Publications & Media Pvt Ltd; Wolters Kluwer
• Subjects: Aging; Alzheimer Disease - diagnosis; Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer's disease; Alzheimer's Disease; Biomarker; Immunotherapy; Tau Imaging; Tau Protein; Transcellular Propagation; Amyloid beta-protein; Animals; Autophagy; Biological markers; Brain research; Care and treatment; Dementia; Diagnosis; Geriatrics; Humans; Immunotherapy; Kinases; Laboratories; Neurodegeneration; Neurodegenerative Diseases - metabolism; Neurology; Neurosciences; Pathogenesis; Pathology; Phosphorylation; Physiology; Prevention; Proteins; Research centers; Review; tau Proteins - metabolism; Tau Imaging; Biomarker; Tau Protein; Alzheimer's Disease; Immunotherapy; Transcellular Propagation
• ISSN: 0366-6999; 2542-5641; 2542-5641
• DOI: 10.4103/0366-6999.220313

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. This review was based on a comprehensive search using online literature databases, including PubMed, Web of Science, and Google Scholar. 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. Amyloid plaques enriched with extracellular amyloid beta (Aβ) and intracellular neurofibrillary tangles comprised of hyperphosphorylated tau proteins are the two main pathological hallmarks of AD. 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 of tau 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. Detecting changes in tau and targeting tau pathology represent a promising lead in the diagnosis and treatment of AD.