| Autor: |
Takahata, Keisuke, Kimura, Yasuyuki, Sahara, Naruhiko, Koga, Shunsuke, Shimada, Hitoshi, Ichise, Masanori, Saito, Fumie, Moriguchi, Sho, Kitamura, Soichiro, Kubota, Manabu, Umeda, Satoshi, Niwa, Fumitoshi, Mizushima, Jin, Morimoto, Yoko, Ming-Rong, Zhang, W. Dickson, Dennis, Mimura, Masaru, Kato, Motoichiro, Suhara, Tetsuya, Higuchi, Makoto, Keisuke, Takahata, Yasuyuki, Kimura, Naruhiko, Sahara, Hitoshi, Shimada, Masanori, Ichise, Sho, Moriguchi, Soichiro, Kitamura, Manabu, Kubota, Satoshi, Umeda, Fumitoshi, Niwa, Zhang, Ming-Rong, Masaru, Mimura, Motoichiro, Kato, Tetsuya, Suhara, Makoto, Higuchi |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Zdroj: |
BRAIN. 142(10):3265-3279 |
| ISSN: |
0006-8950 |
| Popis: |
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 |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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