Sérrière Sophie, Tauber Clovis, Vercouillie Johnny, Mothes Céline, Pruckner Christelle, Guilloteau Denis, Kassiou Michael, Doméné Aurélie, Garreau Lucette, Page Guylène, Chalon Sylvie
UMR Inserm U930, Université François-Rabelais de Tours, Tours, France.
Laboratoires Cyclopharma, Tours, France.
Neurobiol Aging. 2015 Apr;36(4):1639-1652. doi: 10.1016/j.neurobiolaging.2014.11.023. Epub 2015 Jan 16.
We studied concomitantly the level of neuroinflammation and β-amyloid (Aβ) load in the APPswePS1dE9 transgenic mouse model of Alzheimer's disease using positron emission tomography. The translocator protein 18 kDa (TSPO) tracer [(18)F]DPA-714 was used to measure neuroinflammation and [(18)F]AV-45 for Aβ load in mice at 6, 9, 12, 15, and 19 months of age. At 19 months, we also analyzed the neuroinflammatory and neuroanatomic status of mice brains. The main affected brain areas were the cortex and hippocampus, with a concomitant progression of neuroinflammation with increased amyloid burden. At 19 months, no increase in TSPO binding was observed in the cerebellum; immunostaining revealed W0-2-positive plaques, indicating that the amyloid deposits seemed not stimulate inflammation. This finding was in agreement with the observed level of microglia and astrocytes staining. Our findings provide a better understanding of the relationships between neuroinflammation and plaque accumulation in the course of the disease in this mouse model. The monitoring of both processes should be of value to validate potential therapeutic approaches.
我们使用正电子发射断层扫描技术，同时研究了阿尔茨海默病APPswePS1dE9转基因小鼠模型中的神经炎症水平和β-淀粉样蛋白（Aβ）负荷。使用转运蛋白18 kDa（TSPO）示踪剂[(18)F]DPA - 714测量神经炎症，使用[(18)F]AV - 45测量6、9、12、15和19月龄小鼠的Aβ负荷。在19月龄时，我们还分析了小鼠大脑的神经炎症和神经解剖学状态。主要受影响的脑区是皮层和海马体，神经炎症随着淀粉样蛋白负担的增加而同步进展。在19月龄时，小脑未观察到TSPO结合增加；免疫染色显示有W0 - 2阳性斑块，表明淀粉样蛋白沉积似乎未刺激炎症。这一发现与观察到的小胶质细胞和星形胶质细胞染色水平一致。我们的研究结果有助于更好地理解该小鼠模型疾病过程中神经炎症与斑块积累之间的关系。对这两个过程的监测对于验证潜在的治疗方法应该具有重要价值。
