Advances and considerations in AD tau-targeted immunotherapy

被引:79
作者
Bittar, Alice [1 ]
Bhatt, Nemil [2 ]
Kayed, Rakez [1 ]
机构
[1] Univ Texas Med Branch, Dept Neurol, Mitchell Ctr Neurodegenerat Dis, 301 Univ Blvd, Galveston, TX 77555 USA
[2] Univ Texas Med Branch, Dept Neurosci Cell Biol & Anat, Grad Sch Biomed Sci, 301 Univ Blvd, Galveston, TX 77555 USA
基金
美国国家卫生研究院;
关键词
Tau-targeted immunotherapy; Tau; Amyloid Beta immunotherapy; Alzheimer's disease; Biomarkers extracellular tau; Alzheimer's disease clinical trials; BLOOD-BRAIN-BARRIER; ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; AMYLOID-BETA; MOUSE MODEL; COGNITIVE DECLINE; MEDIATED NEURODEGENERATION; PASSIVE-IMMUNIZATION; EXTRACELLULAR TAU; PHOSPHO-TAU;
D O I
10.1016/j.nbd.2019.104707
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The multifactorial and complex nature of Alzheimer's disease (AD) has made it difficult to identify therapeutic targets that are causally involved in the disease process. However, accumulating evidence from experimental and clinical studies that investigate the early disease process point towards the required role of tau in AD etiology. Importantly, a large number of studies investigate and characterize the plethora of pathological forms of tau protein involved in disease onset and propagation. Immunotherapy is one of the most clinical approaches anticipated to make a difference in the field of AD therapeutics. Tau targeted immunotherapy is the new direction after the failure of amyloid beta (A beta)-targeted immunotherapy and the growing number of studies that highlight the A beta-independent disease process. It is now well established that immunotherapy alone will most likely be insufficient as a monotherapy. Therefore, this review discusses updates on tau-targeted immunotherapy studies, AD-relevant tau species, updates on promising biomarkers and a prospect on combination therapies to surround the disease propagation in an efficient and timely manner.
引用
收藏
页数:11
相关论文
共 139 条
[51]   Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's Disease [J].
Kametani, Fuyuki ;
Hasegawa, Masato .
FRONTIERS IN NEUROSCIENCE, 2018, 12
[52]   Characterization of Early Pathological Tau Conformations and Phosphorylation in Chronic Traumatic Encephalopathy [J].
Kanaan, Nicholas M. ;
Cox, Kristine ;
Alvarez, Victor E. ;
Stein, Thor D. ;
Poncil, Sharra ;
Mckee, Ann C. .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2016, 75 (01) :19-34
[53]   C-Terminally Truncated Forms of Tau, But Not Full-Length Tau or Its C-Terminal Fragments, Are Released from Neurons Independently of Cell Death [J].
Kanmert, Daniel ;
Cantlon, Adam ;
Muratore, Christina R. ;
Jin, Ming ;
O'Malley, Tiernan T. ;
Lee, Gloria ;
Young-Pearse, Tracy L. ;
Selkoe, Dennis J. ;
Walsh, Dominic M. .
JOURNAL OF NEUROSCIENCE, 2015, 35 (30) :10851-10865
[54]  
Kaplan J., 2017, Alzheimer's. Dement, V13, P592
[55]   Tau seeding activity begins in the transentorhinal/entorhinal regions and anticipates phospho-tau pathology in Alzheimer's disease and PART [J].
Kaufman, Sarah K. ;
Del Tredici, Kelly ;
Thomas, Talitha L. ;
Braak, Heiko ;
Diamond, Marc I. .
ACTA NEUROPATHOLOGICA, 2018, 136 (01) :57-67
[56]  
Kerchner G.A., 2017, ALZHEIM DEMENT, V13, DOI [10.1016/j.jalz.2017.07.243.P601, DOI 10.1016/J.JALZ.2017.07.243.P601]
[57]   Neurofilaments as biomarkers in neurological disorders [J].
Khalil, Michael ;
Teunissen, Charlotte E. ;
Otto, Markus ;
Piehl, Fredrik ;
Sormani, Maria Pia ;
Gattringer, Thomas ;
Barro, Christian ;
Kappos, Ludwig ;
Comabella, Manuel ;
Fazekas, Franz ;
Petzold, Axel ;
Blennow, Kaj ;
Zetterberg, Henrik ;
Kuhle, Jens .
NATURE REVIEWS NEUROLOGY, 2018, 14 (10) :577-589
[58]  
Kolarova M., 2016, ALZHEIM DEMENT, V12, pP398, DOI [10.1016/j.jalz.2016.06.751, DOI 10.1016/J.JALZ.2016.06.751]
[59]   Antibody against early driver of neurodegeneration cis P-tau blocks brain injury and tauopathy [J].
Kondo, Asami ;
Shahpasand, Koorosh ;
Mannix, Rebekah ;
Qiu, Jianhua ;
Moncaster, Juliet ;
Chen, Chun-Hau ;
Yao, Yandan ;
Lin, Yu-Min ;
Driver, Jane A. ;
Sun, Yan ;
Wei, Shuo ;
Luo, Man-Li ;
Albayram, Onder ;
Huang, Pengyu ;
Rotenberg, Alexander ;
Ryo, Akihide ;
Goldstein, Lee E. ;
Pascual-Leone, Alvaro ;
McKee, Ann C. ;
Meehan, William ;
Zhou, Xiao Zhen ;
Lu, Kun Ping .
NATURE, 2015, 523 (7561) :431-U118
[60]   Antibody-Derived In Vivo Imaging of Tau Pathology [J].
Krishnaswamy, Senthilkumar ;
Lin, Yan ;
Rajamohamedsait, Wajitha J. ;
Rajamohamedsait, Hameetha B. ;
Krishnamurthy, Pavan ;
Sigurdsson, Einar M. .
JOURNAL OF NEUROSCIENCE, 2014, 34 (50) :16835-16850