WEKO3
アイテム
Associations of the tau protein and oxidative stress to apathy levels in patients with progressive supranuclear palsy.
https://repo.qst.go.jp/records/81517
https://repo.qst.go.jp/records/8151768c374c2-46d3-464e-9f56-bef7bebe5be3
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-01-04 | |||||
| タイトル | ||||||
| タイトル | Associations of the tau protein and oxidative stress to apathy levels in patients with progressive supranuclear palsy. | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Matsuoka, Kiwamu
× Matsuoka, Kiwamu× Takado, Yuhei× Tagai, Kenji× Kubota, Manabu× Sano, Yasunori× Takahata, Keisuke× Ono, Maiko× Seki, Chie× Matsumoto, Hideki× Endo, Hironobu× Shinoto, Hitoshi× Kawamura, Kazunori× Ming-Rong, Zhang× Shimada, Hitoshi× Higuchi, Makoto× Matsuoka, Kiwamu× Takado, Yuhei× Tagai, Kenji× Kubota, Manabu× Sano, Yasunori× Takahata, Keisuke× Ono, Maiko× Seki, Chie× Matsumoto, Hideki× Endo, Hironobu× Shinoto, Hitoshi× Kawamura, Kazunori× Ming-Rong, Zhang× Shimada, Hitoshi× Higuchi, Makoto |
|||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Introduction: Progressive supranuclear palsy (PSP) is one of the primary tauopathies. More than half of the patients with PSP present apathy, defined by diminished goal-directed behavior and cognition and concomitant emotions. While previous studies claimed that apathy is associated with impairment of the anterior brain regions, there is no evidence for the association among tau protein, oxidative stress (OS) as underlying mechanisms of apathy in the posterior brain regions. 1 We hypothesized that tau protein causes OS leading to brain vulnerability and apathy. To test this hypothesis, we performed positron emission tomography (PET) scans with a tau PET ligand, 18F-PM-PBB3 2 and magnetic resonance spectroscopy (MRS) for glutathione (GSH) 3, and volumetry. Materials & Methods: We enrolled 20 PSP patients and 23 healthy controls (HCs). We performed MRS by a short TE spin-echo full-intensity acquired localized single voxel spectroscopy (SPECIAL) sequence (TR/TE/number of excitations = 3000 ms / 8.5 ms / 128), PET scans with a tau PET ligand, 18F-PM-PBB3, and three-dimensional T1-weighted images. Given the importance of both the anterior and posterior cingulate cortex for apathy and GSH , volumes of interest (VOIs) for MRS were manually placed on the anterior cingulate cortex (ACC, 30 × 20 × 20 mm2) and posterior cingulate cortex (PCC, 20 × 20 × 20 mm2) regions (Figure 1). We analyzed MRS data by LCModel software and corrected metabolite values for CSF partial volumes. We examined the correlation of apathy scale (AS) score with the imaging data and the path analysis for models explaining apathy. Results: MRS The average Cramér–Rao lower bound of GSH measurements were 6.1% and 6.9% in ACC and PCC, respectively. While there was no significant difference between the PCC GSH levels of PSP patients and HCs, partial correlation analyses after controlling for age and PSP Rating Scale (PSPRS) scores showed negative correlations between the PCC GSH levels and AS scores (Figure 2). 18F-PM-PBB3 PET In PSP patients, a positive association was found between AS scores and 18F-PM-PBB3 standardized uptake value ratios (SUVRs) in the bilateral angular gyrus (AG) (Figure 3). We found significantly higher 18F-PM-PBB3 SUVRs in the bilateral AG in PSP patients compared with HCs. Partial correlation analyses with age and PSPRS scores as covariates showed negative correlations between the PCC GSH levels and 18F-PM-PBB3 SUVRs in the AG/PCC. Volumetry Voxel-based morphometry (VBM) analysis in PSP patients showed negative associations between AS scores and the GM volumes in the right inferior frontal gyrus (IFG) and the ACC. Path analysis Path analysis generated a well-fitted model between the AS scores, the 18F-PM-PBB3 SUVRs in the AG, the PCC GSH levels, and the GM volumes in the right IFG. Discussion: We found the associations of apathy with tau accumulation levels in the AG, the GSH levels in the PCC, and the brain volumes of the right IFG and ACC. We also found the negative associations between 18F-PM-PBB3 SUVRs in the AG/PCC region and the GSH levels in the PCC, suggesting the link between the tau protein accumulations and OS. Although there was no significant difference in GSH levels between PSP and HCs, our model generated by path analysis suggests that the depletion of GSH in the PCC is associated with the abnormal tau protein in the AG/PCC region, leading to a part of underlying mechanisms of apathy. Antioxidant GSH may serve as the resilience factor of the neural system by limiting the damages from OS caused by tau protein accumulation. Conclusions: The potential link among tau protein, OS, brain atrophies in both the anterior and posterior brain regions as underlying brain mechanisms for apathy in PSP patients was suggested. |
|||||
| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | ISMRM JPC 2020 | |||||
| 発表年月日 | ||||||
| 日付 | 2020-12-12 | |||||
| 日付タイプ | Issued | |||||
