Four-repeat tauopathies.
Progress in Neurobiology. 2019-06-01; : 101644
DOI: 10.1016/j.pneurobio.2019.101644
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Rösler TW(1), Tayaranian Marvian A(1), Brendel M(2), Nykänen NP(3), Höllerhage M(1), Schwarz SC(3), Hopfner F(4), Koeglsperger T(5), Respondek G(1), Schweyer K(1), Levin J(5), Villemagne VL(6), Barthel H(7), Sabri O(7), Müller U(8), Meissner WG(9), Kovacs GG(10), Höglinger GU(11).
Author information:
(1)Dept. of Translational Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany; Dept. of Neurology, Technical University of Munich, School of Medicine, 81675 Munich, Germany.
(2)Dept. of Nuclear Medicine, University of Munich, 81377 Munich, Germany.
(3)Dept. of Translational Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany.
(4)Dept. of Psychiatry, University of Munich, 80336 Munich, Germany.
(5)Dept. of Neurology, University of Munich, 81377 Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany.
(6)Dept. of Molecular Imaging and Therapy, Austin Health, Heidelberg, VIC, 3084, Australia; The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia; Dept. of Medicine, Austin Health,
University of Melbourne, Melbourne, VIC, Australia.
(7)Dept. of Nuclear Medicine, University of Leipzig, 04103 Leipzig, Germany.
(8)Institute for Human Genetics, University of Giessen, 35392 Giessen, Germany.
(9)Service de Neurologie, CHU Bordeaux, 33000 Bordeaux, France; Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; Dept. of Medicine, University of Otago, Christchurch, New Zealand; New Zealand Brain Research Institute, Christchurch, New Zealand.
(10)Institute of Neurology, Medical University of Vienna, 1090 Vienna, Austria; Dept. of Laboratory Medicine and Pathobiology, University of Toronto, Laboratory Medicine Program, University Health Network, Toronto, Canada; Tanz Centre for Research in Neurodegenerative Disease, Krembil Brain Institute, Toronto, Canada.
(11)Dept. of Translational Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany; Dept. of Neurology, Technical University of Munich, School of Medicine, 81675 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany; Dept. of Neurology, Hannover Medical School, 30625 Hannover, Germany. Electronic address: .
Tau is a microtubule-associated protein with versatile functions in the dynamic assembly of the neuronal cytoskeleton. Four-repeat (4R-) tauopathies are a group of neurodegenerative diseases defined by cytoplasmic inclusions predominantly composed of tau protein isoforms with four microtubule-binding domains. Progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease or glial globular tauopathy belong to the group of 4R-tauopathies. The present review provides an introduction in the current concept of 4R-tauopathies, including an overview of the neuropathological and clinical spectrum of these diseases. It describes the genetic and environmental etiological factors, as well as the contemporary knowledge about the pathophysiological mechanisms, including post-translational modifications, aggregation and fragmentation of tau, as well as the role of protein degradation mechanisms. Furthermore, current theories about disease propagation are discussed, involving different extracellular tauspecies and their cellular release and uptake mechanisms. Finally, molecular diagnostic tools for 4R-tauopathies, including tau-PET and fluid biomarkers, and investigational therapeutic strategies are presented. In summary, we report on 4R-tauopathies as overarching disease concept based on a shared pathophysiological concept, and highlight the challenges and opportunities on the way towards a causal therapy.
Copyright © 2019 Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.pneurobio.2019.101644
PMID: 31238088