Matsuda Hiroshi, Hanyu Haruo, Kaneko Chikako, Ogura Masato, Yamao Tensho
Drug Discovery and Cyclotron Research Center, Southern Tohoku Research Institute for Neuroscience, 7-61-2 Yatsuyamada, Koriyama, Fukushima, 963-8052, Japan.
Department of Biofunctional Imaging, Fukushima Medical University, 1 Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan.
Ann Nucl Med. 2025 May;39(5):458-465. doi: 10.1007/s12149-025-02018-7. Epub 2025 Jan 28.
This study aims to accurately classify ATN profiles using highly specific amyloid and tau PET ligands and MRI in patients with cognitive impairment and suspected Alzheimer's disease (AD). It also aims to explore the relationship between quantified amyloid and tau deposition and cognitive function.
Twenty-seven patients (15 women and 12 men; age range: 64-81 years) were included in this study. Amyloid and tau PET scans were performed using F-NAV4694 and F-MK6240, respectively. For each patient, amyloid and tau PET images were visually assessed and classified as either amyloid-positive or amyloid-negative, and as F-MK6240 Braak stage 0 (tau-negative) or Braak stages I-VI (tau-positive). Voxel-based morphometry of three-dimensional T1-weighted MRI was used to evaluate neurodegeneration. Amyloid and tau depositions were quantified using the Centiloid scale and standardized uptake value ratio (SUVR), respectively. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE).
Patients were categorized into seven ATN profiles. Six patients (22%) exhibited a normal AD biomarker profile, 15 patients (56%) fell within the Alzheimer's continuum, and 14 patients (52%) were diagnosed with AD. Additionally, six patients (22%) displayed non-AD pathological changes. Positive and negative findings of amyloid and tau PET were concordant in 24 patients (89%). Among the 14 patients diagnosed with AD, the Centiloid scale for amyloid deposition did not show a significant negative correlation with MMSE scores (r = 0.269, p = 0.451). In contrast, the SUVR for tau deposition in the neocortex exhibited a significant negative correlation (r = -0.689, p = 0.014), while tau deposition in the mesial temporal region did not show a significant correlation (r = 0.158, p = 0.763).
Highly specific amyloid and tau PET scans, along with MRI, can be utilized to accurately classify ATN profiles in patients with cognitive impairment and suspected AD. The discordance in amyloid and tau PET findings in three patients allowed for a more precise AD diagnosis. Furthermore, tau PET imaging provided insight into the propagation of tau deposition in the neocortex beyond the mesial temporal region, which is associated with cognitive decline.
本研究旨在使用高度特异性的淀粉样蛋白和tau蛋白PET配体以及MRI对认知障碍和疑似阿尔茨海默病（AD）患者的ATN（淀粉样蛋白、tau蛋白和神经退行性变）特征进行准确分类。本研究还旨在探索定量的淀粉样蛋白和tau蛋白沉积与认知功能之间的关系。
本研究纳入了27例患者（15例女性和12例男性；年龄范围：64 - 81岁）。分别使用F-NAV4694和F-MK6240进行淀粉样蛋白和tau蛋白PET扫描。对每位患者的淀粉样蛋白和tau蛋白PET图像进行视觉评估，并分类为淀粉样蛋白阳性或淀粉样蛋白阴性，以及F-MK6240 Braak分期0期（tau蛋白阴性）或Braak分期I - VI期（tau蛋白阳性）。使用基于体素的三维T1加权MRI形态学测量来评估神经退行性变。分别使用Centiloid量表和标准化摄取值比（SUVR）对淀粉样蛋白和tau蛋白沉积进行定量。使用简易精神状态检查表（MMSE）评估整体认知功能。
患者被分为七种ATN特征类型。6例患者（22%）表现出正常的AD生物标志物特征，15例患者（56%）处于阿尔茨海默病连续谱范围内，14例患者（52%）被诊断为AD。此外，6例患者（22%）表现出非AD病理变化。24例患者（89%）的淀粉样蛋白和tau蛋白PET检查的阳性和阴性结果一致。在14例被诊断为AD的患者中，淀粉样蛋白沉积的Centiloid量表与MMSE评分之间未显示出显著的负相关（r = 0.269，p = 0.451）。相比之下，新皮质中tau蛋白沉积的SUVR显示出显著的负相关（r = -0.689，p = 0.014），而内侧颞叶区域的tau蛋白沉积未显示出显著相关性（r = 0.158，p = 0.763）。
高度特异性的淀粉样蛋白和tau蛋白PET扫描以及MRI可用于准确分类认知障碍和疑似AD患者的ATN特征。3例患者淀粉样蛋白和tau蛋白PET检查结果不一致，这有助于更精确地诊断AD。此外，tau蛋白PET成像揭示了tau蛋白沉积在新皮质中超出内侧颞叶区域的传播情况，这与认知功能下降相关。
