Translocator protein (TSPO) is a mitochondrial protein expressed by microglia, ligands for which are used as a marker of neuroinflammation in PET studies of Alzheimer’s disease (AD). We previously showed increasing TSPO load in the cerebral cortex with AD progression, consistent with TSPO PET scan findings. Here, we aim to characterise the microglial phenotype associated with TSPO expression to aid interpretation of the signal generated by TSPO ligands in patients. Human post-mortem sections of temporal lobe (TL) and cerebellum (Cb) from cases classified by Braak group (0–II, III–IV, V–VI; each n = 10) were fluorescently double labelled for TSPO and microglial markers: Iba1, HLA-DR, CD68, MSR-A and CD64. Quantification was performed on scanned images using QuPath software to assess the microglial phenotype of TSPO. Qualitative analysis was also performed for TSPO with GFAP (astrocytes), CD31 (endothelial cells) and CD163 (perivascular macrophages) to characterise the cellular profile of TSPO. The percentage of CD68⁺TSPO⁺ double-labelled cells was significantly higher than for other microglial markers in both brain regions and in all Braak stages, followed by MSR-A⁺TSPO⁺ microglia. Iba1⁺TSPO⁺ cells were more numerous in the cerebellum than the temporal lobe, while CD64⁺TSPO⁺ cells were more numerous in the temporal lobe. No differences were observed for the other microglial markers. TSPO expression was also detected in endothelial cells, but not detected in astrocytes nor in perivascular macrophages. Our data suggest that TSPO is mainly related to a phagocytic profile of microglia (CD68⁺) in human AD, potentially highlighting the ongoing neurodegeneration.

转运蛋白 （TSPO） 是一种由小胶质细胞表达的线粒体蛋白，其配体在阿尔茨海默病 （AD） 的 PET 研究中用作神经炎症的标志物。我们之前显示，随着 AD 的进展，大脑皮层的 TSPO 负荷增加，与 TSPO PET 扫描结果一致。在这里，我们旨在表征与 TSPO 表达相关的小胶质细胞表型，以帮助解释 TSPO 配体在患者中产生的信号。按 Braak 组 （0-II、III-IV、V-VI;每个 n = 10） 分类的病例的颞叶 （TL） 和小脑 （Cb） 的人类尸检切片对 TSPO 和小胶质细胞标志物：Iba1、HLA-DR、CD68、MSR-A 和 CD64 进行荧光双标记。使用 QuPath 软件对扫描图像进行定量，以评估 TSPO 的小胶质细胞表型。还用 GFAP （星形胶质细胞） 、 CD31 （内皮细胞） 和 CD163 （血管周围巨噬细胞） 对 TSPO 进行了定性分析，以表征 TSPO 的细胞特征。在两个脑区和所有 Braak 阶段，CD68 ⁺ TSPO ⁺ 双标记细胞的百分比显著高于其他小胶质细胞标志物，其次是 MSR-A ⁺ TSPO ⁺ 小胶质细胞。Iba1 ⁺ TSPO ⁺ 细胞在小脑中比在颞叶中更多，而 CD64 ⁺ TSPO ⁺ 细胞在颞叶中更多。其他小胶质细胞标志物未观察到差异。在内皮细胞中也检测到 TSPO 表达，但在星形胶质细胞和血管周围巨噬细胞中未检测到。我们的数据表明，TSPO 主要与人类 AD 中小胶质细胞 （CD68⁺） 的吞噬特征有关，可能突出了正在进行的神经退行性变。