Rauchmann Boris-Stephan, Ersözlü Ersin, Luedecke Dorothea, Franzmeier Nicolai, Perneczky Robert
Department of Neuroradiology, LMU Hospital, LMU Munich, Munich, Germany.
Division of Mental Health of Older Adults, Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität München, Nußbaumstr. 7, 80336, Munich, Germany.
Sci Rep. 2025 May 25;15(1):18142. doi: 10.1038/s41598-025-98338-9.
Neuropathological and neuroimaging studies have identified several (endo-)phenotypes of Alzheimer's disease (AD), suggesting a substantial heterogeneity in cerebral atrophy and tau spreading patterns. We included in our study a total of 320 participants, including healthy controls (N = 154) and patients across the AD spectrum (N = 166). We identified clusters of cerebral atrophy and tau PET uptake using a data-driven and similarity-based clustering approach, aiming to examine regional abnormality patterns in both modalities and differences in the clinical, cognitive, and biomarker characteristics among derived clusters. Abnormality patterns in tau PET and T1-weighted MRI within the same individuals revealed four distinct clusters for each imaging modality as surrogate markers of tau and neurodegeneration, respectively. The tau PET and atrophy clusters mainly showed substantial differences in their clustering allocations. While having the most severe biomarkers burden, the left temporal tau and diffuse atrophy clusters revealed the fastest clinical progression and steepest increase in tau PET uptake. Moreover, the diffuse atrophy cluster showed the fastest cortical volume loss, followed by the limbic-predominant atrophy cluster. Our results suggest characteristic differences between tau PET and atrophy clusters, especially for tau PET clusters, revealing more pronounced differences in cognitive profiles and disease biomarker trajectories than atrophy clusters.
神经病理学和神经影像学研究已经确定了阿尔茨海默病（AD）的几种（内）表型，这表明脑萎缩和tau蛋白扩散模式存在很大的异质性。我们的研究共纳入了320名参与者，包括健康对照者（N = 154）和AD谱系中的患者（N = 166）。我们使用数据驱动且基于相似性的聚类方法确定了脑萎缩和tau蛋白PET摄取的聚类，旨在研究两种模式下的区域异常模式以及衍生聚类之间在临床、认知和生物标志物特征方面的差异。同一受试者体内tau蛋白PET和T1加权MRI的异常模式分别显示，每种成像模式都有四个不同的聚类，作为tau蛋白和神经退行性变的替代标志物。tau蛋白PET聚类和萎缩聚类在聚类分配上主要表现出显著差异。虽然左颞叶tau蛋白和弥漫性萎缩聚类的生物标志物负担最为严重，但它们显示出最快的临床进展和tau蛋白PET摄取的最急剧增加。此外，弥漫性萎缩聚类的皮质体积损失最快，其次是边缘系统为主的萎缩聚类。我们的结果表明tau蛋白PET聚类和萎缩聚类之间存在特征差异，尤其是tau蛋白PET聚类，与萎缩聚类相比，其在认知特征和疾病生物标志物轨迹方面表现出更明显的差异。
