Microglia display modest phagocytic capacity for extracellular tau oligomers.

Petra Majerova,Michal Novak,Branislav Kovacech,Zuzana Kazmerova,Norbert Zilka,Monika Zilkova,Kristina Paholikova,Andrej Kovac

doi:10.1186/s12974-014-0161-z

Petra Majerova, Michal Novak + Show 6 more

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https://doi.org/10.1186/s12974-014-0161-z

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Abstract

BackgroundAbnormal misfolded tau protein is a driving force of neurofibrillary degeneration in Alzheimer’s disease. It has been shown that tau oligomers play a crucial role in the formation of intracellular neurofibrillary tangles. They are intermediates between soluble tau monomers and insoluble tau filaments and are suspected contributors to disease pathogenesis. Oligomeric tau can be released into the extracellular space and spread throughout the brain. This finding opens the question of whether brain macrophages or blood monocytes have the potential to phagocytose extracellular oligomeric tau.MethodsWe have used stable rat primary microglial cells, rat peripheral monocytes-derived macrophages, BV2 microglial and TIB67 macrophage immortalized cell lines that were challenged by tau oligomers prepared by an in vitro aggregation reaction. The efficiency of cells to phagocytose oligomeric protein was evaluated with confocal microscopy. The ability to degrade tau protein was analyzed by immunoblotting.ResultsConfocal microscopy analyses showed that macrophages were significantly more efficient in phagocytosing oligomerized tau proteins than microglial cells. In contrast to macrophages, microglia are able to degrade the internalized oligomeric tau only after stimulation with lipopolysaccharide (LPS).ConclusionsOur data suggests that microglia may not be the principal phagocytic cells able to target extracellular oligomeric tau. We found that peripheral macrophages display a high potency for elimination of oligomeric tau and therefore could play an important role in the modulation of neurofibrillary pathology in Alzheimer’s disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-014-0161-z) contains supplementary material, which is available to authorized users.

Highlights

Abnormal misfolded tau protein is a driving force of neurofibrillary degeneration in Alzheimer’s disease
Simard et al [10] showed that circulating cells such as monocytes could be responsible for effective phagocytosis and degradation of amyloid plaques in transgenic Alzheimer’s disease (AD) mice
In this study we found that peripheral blood monocytederived macrophages (PB-MoM) and immortalized TIB67 macrophages are more proficient in the phagocytosis and degradation of oligomerized truncated tau than primary microglial cells or immortalized BV2 microglia

Summary

Introduction

Abnormal misfolded tau protein is a driving force of neurofibrillary degeneration in Alzheimer’s disease. It has been shown that tau oligomers play a crucial role in the formation of intracellular neurofibrillary tangles. They are intermediates between soluble tau monomers and insoluble tau filaments and are suspected contributors to disease pathogenesis. Oligomeric tau can be released into the extracellular space and spread throughout the brain. This finding opens the question of whether brain macrophages or blood monocytes have the potential to phagocytose extracellular oligomeric tau. It has been hypothesized that macrophages which infiltrate the brain could be more effective in the recognition and subsequent elimination of the pathological lesions than resident microglia [9]. Peripheral macrophages were found to be efficient in phagocytosing synthetic Aβ peptides [11]

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