Satoh Ryota, Utianski Rene L, Duffy Joseph R, Clark Heather M, Stephens Yehkyoung C, Lee Jeyeon, Baker Matt, Rademakers Rosa, Lowe Val J, Josephs Keith A, Whitwell Jennifer L
Department of Radiology.
Department of Neurology, Mayo Clinic, Rochester, MN.
Clin Nucl Med. 2025 Aug 1;50(8):731-742. doi: 10.1097/RLU.0000000000005962. Epub 2025 Jul 2.
Progressive apraxia of speech (PAOS) is a neurodegenerative disorder most commonly arising from a 4-repeat tauopathy that affects the programming or planning of speech, although many patients develop a Parkinson-plus syndrome. The role of neuroinflammation as a disease mechanism is unknown. We investigated the spatial pattern of neuroinflammation in PAOS using PET and evaluated whether it is associated with disease severity, presence of Parkinson-plus features, and tau PET uptake.
Twenty-five PAOS patients (13 with Parkinson-plus features) and 30 controls underwent inflammatory 11C-ER176 and tau 18F-flortaucipir PET scans as well as detailed clinical assessments. Multiple linear regression analyses compared the inflammatory standardized uptake value ratio (SUVR) between PAOS and controls and assessed the relationship with clinical test scores. Pearson correlation analysis examined the relationship between inflammatory and tau SUVRs.
PAOS had greater neuroinflammatory SUVR than controls in the precentral, supplementary motor area, frontal gyri, putamen, pallidum, subthalamic nucleus, and red nucleus (adjusted P < 0.05). Greater neuroinflammation was associated with worse parkinsonism, and patients who had developed Parkinson-plus features showed a broader pattern of neuroinflammation, extending to prefrontal, temporal and parietal cortices. Neuroinflammation correlated with tau uptake in most (96%) PAOS patients (r > 0.3, P < 0.05). The higher correlation was associated with worse parkinsonism (r = 0.61, P < 0.05) and disease severity (r = 0.54, P < 0.05).
11C-ER176 PET analysis demonstrates neuroinflammation in frontal and subcortical regions in PAOS which is particularly severe and widespread with the development of Parkinson-plus clinical features. The colocalization of neuroinflammation and tau may support a relationship between these disease mechanisms.
进行性言语失用症（PAOS）是一种神经退行性疾病，最常见于由4重复tau蛋白病引起，该病影响言语的编程或计划，尽管许多患者会发展为帕金森叠加综合征。神经炎症作为一种疾病机制的作用尚不清楚。我们使用正电子发射断层扫描（PET）研究了PAOS中神经炎症的空间模式，并评估其是否与疾病严重程度、帕金森叠加特征的存在以及tau蛋白PET摄取有关。
25例PAOS患者（13例有帕金森叠加特征）和30名对照者接受了炎症性11C-ER176和tau蛋白18F-氟代托卡朋PET扫描以及详细的临床评估。多元线性回归分析比较了PAOS患者和对照者之间的炎症标准化摄取值比率（SUVR），并评估了其与临床测试分数的关系。Pearson相关分析检查了炎症性SUVR和tau蛋白SUVR之间的关系。
与对照组相比，PAOS患者在中央前回、辅助运动区、额回、壳核、苍白球、丘脑底核和红核中的神经炎症性SUVR更高（校正P<0.05）。更严重的神经炎症与更严重的帕金森症状相关，并且已发展为帕金森叠加特征的患者表现出更广泛的神经炎症模式，延伸至前额叶、颞叶和顶叶皮质。在大多数（96%）PAOS患者中，神经炎症与tau蛋白摄取相关（r>0.3，P<0.05）。更高的相关性与更严重的帕金森症状（r=0.61，P<0.05）和疾病严重程度（r=0.54，P<0.05）相关。
11C-ER176 PET分析显示PAOS患者额叶和皮质下区域存在神经炎症，随着帕金森叠加临床特征的出现，这种炎症尤为严重且广泛。神经炎症和tau蛋白的共定位可能支持这些疾病机制之间的关系。
