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<p>We aimed to compare brain oxidative stress (OS) levels between patients with early Alzheimer’s disease (eAD) and age-matched cognitively normal (CN) individuals using <sup>64</sup>Cu-diacetyl-bis(N4-methylthiosemicarbazone) (<sup>64</sup>Cu-ATSM) PET/MRI. Thirty-seven patients with eAD (71.8±8.0 years) and 14 CN (71.1±7.7 years) were included in this study. They underwent PET/MRI using Pittsburg compound-B (<sup>11</sup>C-PiB) and <sup>64</sup>Cu-ATSM on separate days. Each standardized uptake value (SUV) image was converted to an SUV ratio (SUVR) image using the individual cerebellar SUV as a reference. <sup>11</sup>C-PiB centiloid (CL) scale was calculated from a whole-brain image and compared with other biomarkers. The Patlak plot method was used to calculate the influx rate constant (K<sub>in</sub>) image of <sup>64</sup>Cu-ATSM to evaluate the global and regional brain OS levels. Hippocampal volume was also evaluated using three-dimensional T1-weighted MRI.&#xa0;All eAD patients showed positive PiB accumulation, whereas all CN individuals showed negative accumulation. Significant group differences were found in the Mini-Mental State Examination score, Clinical Dementia Rating (CDR) score, Alzheimer’s Disease Assessment Scale (ADAS), hippocampal volume, and PiB-CL. <sup>64</sup>Cu-ATSM K<sub>in</sub> images showed significant positive correlations with PiB-CL in the hippocampus and posterior cingulate cortex of eAD patients. <sup>64</sup>Cu-ATSM SUVR in the hippocampus was negatively correlated with hippocampal volume, CDR score. A significant positive correlation between <sup>64</sup>Cu-ATSM K<sub>in</sub> and PiB-CL was observed in the regions responsible for eAD, suggesting that increased OS levels in the brain are associated with the progression of amyloid deposition. These findings indicate ⁶⁴Cu-ATSM PET is a useful and promising OS evaluation tool.</p>

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Evaluation of increased oxidative stress in the brain of patients with early Alzheimer’s disease by 64Cu-ATSM PET/MRI

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月22日

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  • Ya’nan Huang,
  • Masamichi Ikawa,
  • Munenobu Nogami,
  • Tetsuya Mori,
  • Akira Makino,
  • Yuki Kitazaki,
  • Tomoyuki Mizuno,
  • Hirotaka Kosaka,
  • Yasushi Kiyono,
  • Yasuhiro Nishiyama,
  • Hidehiko Okazawa

摘要

We aimed to compare brain oxidative stress (OS) levels between patients with early Alzheimer’s disease (eAD) and age-matched cognitively normal (CN) individuals using 64Cu-diacetyl-bis(N4-methylthiosemicarbazone) (64Cu-ATSM) PET/MRI. Thirty-seven patients with eAD (71.8±8.0 years) and 14 CN (71.1±7.7 years) were included in this study. They underwent PET/MRI using Pittsburg compound-B (11C-PiB) and 64Cu-ATSM on separate days. Each standardized uptake value (SUV) image was converted to an SUV ratio (SUVR) image using the individual cerebellar SUV as a reference. 11C-PiB centiloid (CL) scale was calculated from a whole-brain image and compared with other biomarkers. The Patlak plot method was used to calculate the influx rate constant (Kin) image of 64Cu-ATSM to evaluate the global and regional brain OS levels. Hippocampal volume was also evaluated using three-dimensional T1-weighted MRI. All eAD patients showed positive PiB accumulation, whereas all CN individuals showed negative accumulation. Significant group differences were found in the Mini-Mental State Examination score, Clinical Dementia Rating (CDR) score, Alzheimer’s Disease Assessment Scale (ADAS), hippocampal volume, and PiB-CL. 64Cu-ATSM Kin images showed significant positive correlations with PiB-CL in the hippocampus and posterior cingulate cortex of eAD patients. 64Cu-ATSM SUVR in the hippocampus was negatively correlated with hippocampal volume, CDR score. A significant positive correlation between 64Cu-ATSM Kin and PiB-CL was observed in the regions responsible for eAD, suggesting that increased OS levels in the brain are associated with the progression of amyloid deposition. These findings indicate ⁶⁴Cu-ATSM PET is a useful and promising OS evaluation tool.