@misc{oai:repo.qst.go.jp:00067065,
 author = {田桑, 弘之 and 田桑 弘之},
 month = {Nov},
 note = {Accumulation of intracellular neurofibrillary tangles (NFTs) consisting of microtubule-associated protein tau is a major hallmark of Alzheimer’s disease ad related neurodegenerative diseases referred to as tauopathies, while mechanisms underlying tau-mediated neurodegeneration remain unclear. To elucidate molecular and cellular processes mediating the death of neurons bearing NFTs, we conducted in vivo multimodal imaging studies, consisting of PET, MRI and two-photon microscopy of an inducible transgenic mouse model expressing human 0N4R tau with the P301L mutation, termed rTg4510 mice. Longitudinal PET/MRI studies revealed age-dependent pathological tau accumulation, microglial activation and volume reduction in the cortex and hippocampus. We observed plateaued tau pathology, as there was no significant difference in tau PET signals between rTg4510 mice at 7 and 12-14 months of age. Correspondingly, in vivo two-photon microscopy demonstrated a plateaued total amount of tau inclusions after 7 months of age. This was attributed to equilibrium between emergence of new tau inclusions and disappearance of tangle-bearing neurons, and the rates of these two events were significantly reduced by doxycycline-induced suppression of transgenic human P301L tau. Most interestingly, daily two-photon microscopic observations of individual mCherry-expressing neurons and GFP-expressing microglia illustrated engulfment of tangle-burdened neurons by hypertrophic cell bodies or processes of microglia, followed by elimination of these neurons. These data suggest an essential role of phagocytic microglia in tau-induced neuronal death. Further studies are ongoing to search for molecular signals triggering phagocytic microglial activation., 北米神経科学会},
 title = {Engulfment of tangle-bearing neurons by microglia in a living tauopathy model},
 year = {2018}
}