Supplementary Material for: Patterns of Microglial Cell Activation in Alzheimer Disease and Frontotemporal Lobar Degeneration

<b><i>Aims:</i></b> Microglia-driven neuroinflammation can play an important role in the pathophysiology of neurodegenerative disorders. In this study, we sought to characterize the distribution of microglial cell activation in 2 neurodegenerative dementias with distinct protein signatures, Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD) of the TDP subtype, and to determine if there was an anatomical correlation with the phenotypes most commonly associated with these conditions. <b><i>Methods:</i></b> The distribution and extent of microglial cell activation was assessed semiquantitatively in the hippocampal formation, cortical gray matter, and subcortical white matter of CD68-immunostained sections of the frontal, temporal, parietal, and occipital cortices from 15 pathologically confirmed cases of AD, 13 cases of FTLD, and 18 controls. <b><i>Results:</i></b> Significantly higher levels of microglial cell activation occurred in the subiculum in AD and FTLD than in controls. Additionally, AD had higher microglial activation in the CA1 and FTLD in the hippocampal white matter than the controls. Microglial activation was greater in the dentate gyrus molecular layer in AD than in FTLD. In the cortical regions, the 2 pathological groups differed only in frontal white matter, with the FTLD group showing higher microglial scores. FTLD showed higher microglial activation in the white matter compared to the respective gray matter in the entorhinal, temporal, and frontal regions. <b><i>Conclusions:</i></b> Our work expands the knowledge of the distribution and magnitude of microglial activation in these disorders. Additionally, we found some microglial circuit-specific patterns that could help to explain some of the clinical overlap between AD and FTLD-TDP, namely in memory deficits.

<b><i>研究目的：</i></b>小胶质细胞（microglia）介导的神经炎症在神经退行性疾病的病理生理机制中发挥关键作用。本研究旨在系统表征两种具有独特蛋白特征的神经退行性痴呆——阿尔茨海默病（AD）以及TDP亚型额颞叶变性（FTLD）——中小胶质细胞活化的分布特征，并探究其与这两种疾病最常见临床表型的解剖学关联。<b><i>方法：</i></b>本研究对15例经病理证实的AD患者、13例FTLD患者及18例健康对照者的额叶、颞叶、顶叶及枕叶皮层的CD68免疫染色切片进行半定量分析，评估海马结构、皮层灰质及皮层下白质中小胶质细胞活化的分布与程度。<b><i>结果：</i></b>相较于健康对照组，AD组与FTLD组的海马下托区域均出现显著升高的小胶质细胞活化水平。此外，AD组的海马CA1区、FTLD组的海马白质区域的小胶质细胞活化程度均高于对照组；AD组齿状回分子层的小胶质细胞活化程度高于FTLD组。在皮层区域中，两组病理组仅在额叶白质存在差异：FTLD组的小胶质细胞活化评分更高。相较于内嗅皮层、颞叶及额叶的对应灰质区域，FTLD组白质中的小胶质细胞活化程度更高。<b><i>结论：</i></b>本研究拓展了学界对这两种疾病中小胶质细胞活化的分布特征与程度的认知。此外，本研究发现了若干具有环路特异性的小胶质细胞活化模式，这些模式或可用于解释AD与FTLD-TDP之间存在的部分临床重叠特征，尤以记忆障碍为典型。