title: Glial and neuronal tau pathology in tauopathies: characterization of disease-specific phenotypes and tau pathology progression.
abstract: Tauopathies are degenerative diseases characterized by the accumulation of phosphorylated tau in neurons and glial cells. With some exceptions, tau deposits in neurons are mainly manifested as pretangles and tangles unrelated to the tauopathy. It is thought that abnormal tau deposition in neurons occurs following specific steps, but little is known about the progression of tau pathology in glial cells in tauopathies. We compared tau pathology in different astrocyte phenotypes and oligodendroglial inclusions with that in neurons in a large series of tauopathies, including progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease, Pick disease, frontotemporal lobar degenerations (FTLD) associated with mutations in the tau gene, globular glial tauopathy (GGT), and tauopathy in the elderly. Our findings indicate that disease-specific astroglial phenotypes depend on i) the primary amino acid sequence of tau (mutated tau, 3Rtau, and 4Rtau); ii) phospho-specific sites of tau phosphorylation, tau conformation, tau truncation, and ubiquitination in that order (which parallel tau modifications related to pretangle and tangle stages in neurons); and iii) modifications of the astroglial cytoskeleton. In contrast to astrocytes, coiled bodies in oligodendrocytes have similar characteristics whatever the tauopathy, except glial globular inclusions in GGT, and coiled bodies and globular oligodendroglial inclusions in FTLD-tau/K317M. These observations indicate that tau pathology in glial cells largely parallels, but is not identical to, that in neurons in many tauopathies.
authors: From the Institut de Neuropatologia (IF, IL-G, MC, LA), IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, Hospitalet de Llobregat, CIBERNED (Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas); Neurometabolic Disease Lab (ED), IDIBELL-Hospital Universitari de Bellvitge, Hospitalet de LLobregat, CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras); Unitat de Biologia (BT-E), Serveis Cientifics I Tecnics, Universitat de Barcelona, Hospitalet de Llobregat, Spain; Sao Paulo Brain Bank, Brazil (RD); and Institute of Neurology, Medical University of Vienna, Austria (GG-K).
authors: Isidre
authors: I
authors: Ferrer
authors: Irene
authors: I
authors: López-González
authors: Margarita
authors: M
authors: Carmona
authors: Laura
authors: L
authors: Arregui
authors: Esther
authors: E
authors: Dalfó
authors: Benjamin
authors: B
authors: Torrejón-Escribano
authors: Roberta
authors: R
authors: Diehl
authors: Gabor G
authors: GG
authors: Kovacs
mesh_terms: D001921:Brain / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D009457:Neuroglia / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D010641:Phenotype; D024801:Tauopathies / Q000235:genetics / Q000473:pathology*; D016875:tau Proteins / Q000235:genetics
chemical_list: D016875:tau Proteins