@article{oai:repo.qst.go.jp:00076643,
 author = {Takahata, Keisuke and Kimura,, Yasuyuki and Sahara, Naruhiko and Koga,, Shunsuke and Shimada,, Hitoshi and Ichise, Masanori and Saito, Fumie and Moriguchi, Sho and Kitamura, Soichiro and Kubota, Manabu and Umeda, Satoshi and Niwa, Fumitoshi and Mizushima, Jin and Morimoto, Yoko and Ming-Rong, Zhang and W. Dickson, Dennis and Mimura, Masaru and Kato, Motoichiro and Suhara, Tetsuya and Higuchi, Makoto and Keisuke, Takahata and Yasuyuki, Kimura and Naruhiko, Sahara and Hitoshi, Shimada and Masanori, Ichise and Sho, Moriguchi and Soichiro, Kitamura and Manabu, Kubota and Satoshi, Umeda and Fumitoshi, Niwa and Zhang, Ming-Rong and Masaru, Mimura and Motoichiro, Kato and Tetsuya, Suhara and Makoto, Higuchi},
 issue = {10},
 journal = {BRAIN},
 month = {Sep},
 note = {Tau deposits is a core feature of neurodegenerative disorder following traumatic brain injury (TBI). Despite ample evidence from
post-mortem studies demonstrating exposure to both mild-repetitive and severe TBIs are linked to tau depositions, associations of
topology of tau lesions with late-onset psychiatric symptoms due to TBI have not been explored. To address this issue, we assessed
tau deposits in long-term survivors of TBI by PET with 11C-PBB3, and evaluated those associations with late-life neuropsychiatric
outcomes. PET data were acquired from 27 subjects in the chronic stage following mild-repetitive or severe TBI and 15 healthy
control subjects. Among the TBI patients, 14 were diagnosed as having late-onset symptoms based on the criteria of traumatic
encephalopathy syndrome. For quantification of tau burden in TBI brains, we calculated 11C-PBB3 binding capacity (cm3), which
is a summed voxel value of binding potentials (BP*
ND) multiplied by voxel volume. Main outcomes of the present study were
differences in 11C-PBB3 binding capacity between groups, and the association of regional 11C-PBB3 binding capacity with neuropsychiatric
symptoms. To confirm 11C-PBB3 binding to tau deposits in TBI brains, we conducted in vitro PBB3 fluorescence and
phospho-tau antibody immunofluorescence labelling of brain sections of chronic traumatic encephalopathy obtained from the
Brain Bank. Our results showed that patients with TBI had higher 11C-PBB3 binding capacities in the neocortical grey and
white matter segments than healthy control subjects. Furthermore, TBI patients with traumatic encephalopathy syndrome
showed higher 11C-PBB3 binding capacity in the white matter segment than those without traumatic encephalopathy syndrome,
and regional assessments revealed that subgroup difference was also significant in the frontal white matter. 11C-PBB3 binding
capacity in the white matter segment correlated with the severity of psychosis. In vitro assays demonstrated PBB3-positive tau
inclusions at the depth of neocortical sulci, confirming 11C-PBB3 binding to tau lesions. In conclusion, increased 11C-PBB3 binding
capacity is associated with late-onset neuropsychiatric symptoms following TBI, and a close correlation was found between
psychosis and 11C-PBB3 binding capacity in the white matter},
 pages = {3265--3279},
 title = {PET-detectable tau pathology correlates with long-term neuropsychiatric outcomes in patients with traumatic brain injury},
 volume = {142},
 year = {2019}
}