Division of Adult Psychiatry, Department of Psychiatry, University Hospitals of Geneva, Switzerland.
Division of Nuclear medicine, University Hospitals of Geneva, Switzerland.
J Alzheimers Dis. 2020;77(3):1043-1056. doi: 10.3233/JAD-200136.
In vivo PET/SPECT imaging of neuroinflammation is primarily based on the estimation of the 18 kDa-translocator-protein (TSPO). However, TSPO is expressed by different cell types which complicates the interpretation.
The present study evaluates the cellular origin of TSPO alterations in Alzheimer's disease (AD).
The TSPO cell origin was evaluated by combining radioactive imaging approaches using the TSPO radiotracer [125I]CLINDE and fluorescence-activated cell sorting, in a rat model of AD (TgF344-AD) and in AD subjects.
In the hippocampus of TgF344-AD rats, TSPO overexpression not only concerns glial cells but the increase is visible at 12 and 24 months in astrocytes and only at 24 months in microglia. In the temporal cortex of AD subjects, TSPO upregulation involved only glial cells. However, the mechanism of this upregulation appears different with an increase in the number of TSPO binding sites per cell without cell proliferation in the rat, and a microglial cell population expansion with a constant number of binding sites per cell in human AD.
These data indicate an earlier astrocyte intervention than microglia and that TSPO in AD probably is an exclusive marker of glial activity without interference from other TSPO-expressing cells. This observation indicates that the interpretation of TSPO imaging depends on the stage of the pathology, and highlights the particular role of astrocytes.
神经炎症的体内正电子发射断层扫描/单光子发射计算机断层扫描（PET/SPECT）成像主要基于对 18 kDa 转位蛋白（TSPO）的估计。然而，TSPO 由不同的细胞类型表达，这使得解释变得复杂。
本研究评估阿尔茨海默病（AD）中 TSPO 改变的细胞起源。
通过使用 TSPO 放射性示踪剂[125I]CLINDE 和荧光激活细胞分选的放射性成像方法相结合，在 AD 大鼠模型（TgF344-AD）和 AD 患者中评估 TSPO 细胞起源。
在 TgF344-AD 大鼠的海马体中，TSPO 过表达不仅涉及神经胶质细胞，而且在 12 和 24 个月时在星形胶质细胞中可见增加，而仅在 24 个月时在小胶质细胞中可见增加。在 AD 患者的颞叶皮质中，TSPO 上调仅涉及神经胶质细胞。然而，这种上调的机制似乎不同，在大鼠中，每个细胞的 TSPO 结合位点数量增加而没有细胞增殖，而在人类 AD 中，每个细胞的结合位点数量不变但小胶质细胞数量增加。
这些数据表明星形胶质细胞比小胶质细胞更早干预，AD 中的 TSPO 可能是神经胶质活性的特有标志物，而不受其他 TSPO 表达细胞的干扰。这一观察表明，TSPO 成像的解释取决于病理学的阶段，并强调了星形胶质细胞的特殊作用。
