title: Lost after translation: missorting of Tau protein and consequences for Alzheimer disease.
abstract: Tau is a microtubule-associated-protein that is sorted into neuronal axons in physiological conditions. In Alzheimer disease (AD) and other tauopathies, Tau sorting mechanisms fail and Tau becomes missorted into the somatodendritic compartment. In AD, aberrant amyloid-β (Aβ) production might trigger Tau missorting. The physiological axonal sorting of Tau depends on the developmental stage of the neuron, the phosphorylation state of Tau and the microtubule cytoskeleton. Disease-associated missorting of Tau is connected to increased phosphorylation and aggregation of Tau, and impaired microtubule interactions. Disease-causing mechanisms involve impaired transport, aberrant kinase activation, non-physiological interactions of Tau, and prion-like spreading. In this review we focus on the physiological and pathological (mis)sorting of Tau, the underlying mechanisms, and effects in disease.
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Zempel
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; Center of Advanced European Studies and Research (CAESAR), Bonn, Germany; Max Planck Institute for Neurological Research, Hamburg Outstation, c/o Deutsches Elektronen-Synchrotron (DESY), Hamburg, Germany. Electronic address: mand@mpasmb.desy.de.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Mandelkow
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D003599:Cytoskeleton / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016875:tau Proteins