@misc{oai:repo.qst.go.jp:00070537,
 author = {Ono, Maiko and Ki, Hin and Maruyama, Masahiro and Maeda, Jun and Minamihisamatsu, Takeharu and Suhara, Tetsuya and Higuchi, Makoto and 小野 麻衣子 and 季 斌 and 丸山 将浩 and 前田 純 and 南久松 丈晴 and 須原 哲也 and 樋口 真人},
 month = {Sep},
 note = {In Alzheimer's disease, hyperphosphorylated tau proteins assemble into fibri
ls, making up neurofibrillary tangles (NFTs), and are involved in neuronal l
oss. It is hypothesized that packaging of abnormal tau into NFTs protects ne
urons against tau-induced neurodegeneration, while molecular mediators of NF
T formation versus accumulation of neurotoxic, low-order tau assemblies rema
in unidentified. p62 promotes autophagic degradation of ubiquitinated protei
ns, and sequesters them by forming an inclusion body. In mice transgenic for
mutant human P301S tau protein, NFTs are abundantly developed in the spinal
cord and brainstem but are accompanied by only modest neuronal loss in thes
e areas. By contrast, massive neuron death without deposition of NFTs occurs
in the hippocampus. Here, we investigated regional differences in levels of
p62 and their association with tau lesions between the brainstem and hippoc
ampus of P301S and wild-type mice to analyze roles of p62 in the tau pathoge
nesis. Immunoreactivity for p62 was found in brainstem neurons of wild-type 
mice, and this immunolabeling was markedly intensified with accumulation of 
phosphorylated and ubiquitinated tau in P301S mice, indicating recruitment o
f p62 to packaging of hyperphosphorylated and ubiquitinated tau. Meanwhile, 
p62 was barely detectable in somas of hippocampal pyramidal neurons in both 
wild-type and P301S mice. In these hippocampal neurons, diffuse signals of p
hosphorylated tau spatially overlapped with ubiquitin but not p62 immunoreac
tivity. Moreover, autophagic activities in the hippocampus were higher than 
that in the brainstem as assessed by immunoblotting for LC3. These findings 
suggest that p62 and other components of autophagy are constitutively consum
ed at high levels in hippocampal neurons of P301S mice, leading to insuffici
ent reserve capacity for autophagic clearance of hyperphosphorylated tau and
its segregation into inclusions and eventually neurotoxicity by misfolded b
ut unpackaged tau., 第34回日本神経科学大会（Neuro2011）},
 title = {Selective autophagy in neurons and its involvement in the tau pathogenesis},
 year = {2011}
}