Xu Xinru, Mo Xian, Zhang Wen, Liu Dongming, Chen Qian, Lu Jiaming, Zhu Yajing, Chen Jiu, Zhang Xin, Zhu Zhengyang, Chen Yingxin, Shi Qingxue, Dai Yingxin, Liu Miao, Tong Yanan, Zhang Jinghua, Zhang Guoxu, Wang Zhiguo, Zhang Bing
Department of Radiology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China.
Department of Nuclear Medicine, General Hospital of Northern Theater Command, Shenyang, Liaoning Province, China.
J Alzheimers Dis. 2025 Apr;104(4):1092-1102. doi: 10.1177/13872877251322539. Epub 2025 Mar 21.
BackgroundTau pathology is closely associated with brain atrophy and cognitive decline, but how it specifically influences local and distant gray matter volume (GMV) and cognitive function remains unclear.ObjectiveThis study aims to explore the spatial relationships between tau pathology, GMV and cognition using hybrid positron emission tomography/magnetic resonance imaging (PET/MRI).MethodsTwenty amyloid-β (Aβ)-positive Alzheimer's disease (AD) patients, 14 mild cognitive impairment (MCI) patients, and 22 Aβ-negative normal controls (NC) underwent standardized neuropsychological assessments and F-fortaucipir PET/MRI scans. We investigated the associations between regional tau standardized uptake value ratio (SUVR) and GMV in AD signature regions. Mediation analyses were conducted to explore the potential mediating effects of local and distant GMV in the relationship between tau pathology and cognition.ResultsThe study indicated that increased F-fortaucipir SUVR and decreased GMV were related to cognitive performance in MCI and AD patients. Compared to NC group, the number of brain regions with local and distant correlations between GMV and SUVR was greater in AD/MCI group. Mediation analysis revealed that GMV served as a significant mediator between tau pathology and cognition in local regions. Furthermore, distant effects were also observed, with hippocampal atrophy partially mediated the relationship between entorhinal cortex tau pathology and cognition. Meanwhile, medial parietal lobe atrophy partially mediated the relationship between medial temporal lobe tau deposition and cognition.ConclusionsOur findings provide an anatomically detailed insight into relationships between tau, GMV and cognition, especially in entorhinal cortex-hippocampus, temporal-parietal lobe cortical circuits.
背景
tau蛋白病理改变与脑萎缩和认知功能衰退密切相关，但tau蛋白如何具体影响局部及远距离灰质体积（GMV）和认知功能仍不清楚。
目的
本研究旨在使用正电子发射断层扫描/磁共振成像（PET/MRI）融合技术，探索tau蛋白病理改变、GMV和认知之间的空间关系。
方法
20例淀粉样β蛋白（Aβ）阳性的阿尔茨海默病（AD）患者、14例轻度认知障碍（MCI）患者和22例Aβ阴性的正常对照（NC）接受了标准化神经心理学评估和F-氟代托品PET/MRI扫描。我们研究了AD特征区域中局部tau标准化摄取值比率（SUVR）与GMV之间的关联。进行中介分析以探讨局部和远距离GMV在tau蛋白病理改变与认知关系中的潜在中介作用。
结果
研究表明，F-氟代托品SUVR升高和GMV降低与MCI和AD患者的认知表现相关。与NC组相比，AD/MCI组中GMV与SUVR之间存在局部和远距离相关性的脑区数量更多。中介分析显示，GMV在局部区域的tau蛋白病理改变与认知之间起显著中介作用。此外，还观察到远距离效应，海马萎缩部分介导了内嗅皮质tau蛋白病理改变与认知之间的关系。同时，顶叶内侧萎缩部分介导了颞叶内侧tau蛋白沉积与认知之间的关系。
结论
我们的研究结果为tau蛋白、GMV和认知之间的关系提供了详细的解剖学见解，特别是在内嗅皮质-海马、颞叶-顶叶皮质回路方面。
