PET-detectable tau pathology correlates with long-term neuropsychiatric outcomes in patients with traumatic brain injury

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

書誌情報

BRAIN

巻 142, 号 10, p. 3265-3279, 発行日 2019-09

出版者

Oxford University Press

ISSN

収録物識別子タイプ

ISSN

収録物識別子

0006-8950

PubMed番号

識別子タイプ

PMID

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2023-05-15 17:35:36.006815

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