title: Direct Evidence of Internalization of Tau by Microglia In Vitro and In Vivo.
abstract: The microtubule-associated protein (MAP) tau plays a critical role in the pathogenesis of tauopathies. Excess tau can be released into the extracellular medium in a physiological or pathological manner to be internalized by surrounding neurons-a process that contributes to the spread of this protein throughout the brain. Such spreading may correlate with the progression of the abovementioned diseases. In addition to neurons, tau can be internalized into other cells. Here we demonstrate that microglia take up tau in vitro and in vivo. In this regard, microglia from primary cultures internalized soluble (human recombinant tau42) and insoluble (homogenates derived from human AD brain) tau in vitro. Furthermore, using stereotaxic injection of tau in mice in vivo, we show that murine microglia internalize human tau. In addition, we demonstrate, for the first time, that microglia colocalize with various forms of tau in postmortem brain tissue of patients with Alzheimer's disease and non-demented control subjects. Our data reveal a potential role of microglia in the internalization of tau that might be relevant for the design of strategies to enhance the clearance of extracellular tau in neurodegenerative diseases characterized by the accumulation of this protein.
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.|Centro de Biología Molecular "Severo Ochoa" CSIC-UAM, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Bolós
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.|Centro de Biología Molecular "Severo Ochoa" CSIC-UAM, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Llorens-Martín
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.|Centro de Biología Molecular "Severo Ochoa" CSIC-UAM, Madrid, Spain.
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Jurado-Arjona
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.|Centro de Biología Molecular "Severo Ochoa" CSIC-UAM, Madrid, Spain.
authors.forename: Félix
authors.initials: F
authors.lastname: Hernández
authors.affiliation: Neuropathology Department, CIEN Foundation, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Rábano
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.|Centro de Biología Molecular "Severo Ochoa" CSIC-UAM, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Avila
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000378:metabolism*; D010766:Phosphorylation; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D013997:Time Factors; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D016875:tau Proteins
keywords: Alzheimer’s disease; clearance; microglia; tau protein; tauopathies