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Direct Evidence of Internalization of Tau by Microglia in Vitro and in Vivo

AuthorsBolós, Marta; Llorens-Martín, M. ; Jurado-Arjona, Jerónimo ; Hernández Pérez, Félix ; Rábano, Alberto; Ávila, Jesús
Tau protein
Alzheimer’s disease
Issue Date30-Nov-2015
PublisherIOS Press
CitationJournal of Alzheimer's Disease 50: 77- 87 (2015)
AbstractThe 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.
Identifiersdoi: 10.3233/JAD-150704
issn: 1875-8908
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