Early and Longitudinal Microglial Activation but Not Amyloid Accumulation Predicts Cognitive Outcome in PS2APP Mice
Early and Longitudinal Microglial Activation but Not Amyloid Accumulation Predicts Cognitive Outcome in PS2APP Mice
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DOI：
10.2967/jnumed.118.217703
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发表时间：
2019-04-01
影响因子：
9.3
通讯作者：
Brendel, Matthias
中科院分区：
文献类型：
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作者：
Focke, Carola;Blume, Tanja;Brendel, Matthias
神经炎症可能对阿尔茨海默病（AD）患者的认知结果有有益或有害的净影响。PET成像与18kda转运蛋白（TSPO）可以纵向监测体内小胶质细胞的激活。方法：对8 ~ 13月龄AD转基因小鼠模型（PS2APP）进行终末认知评估（水迷宫），收集TSPO和淀粉样蛋白的连续PET测量，然后对小胶质细胞、淀粉样蛋白和突触密度进行免疫组织化学分析。结果：PS2APP小鼠在8月龄时较高的TSPO表达预示着更好的认知结果和更高的突触密度。TSPO激活到13月龄的进展也显示出与保留认知的中度关联，但淀粉样变与认知结果无关，无论在哪个时间点。结论：在AD小鼠模型中，纵向TSPO和淀粉样PET结合终末认知测试进行的首次PET研究表明，持续的小胶质细胞反应似乎赋予了保留的认知能力。
Neuroinflammation may have beneficial or detrimental net effects on the cognitive outcome of Alzheimer disease (AD) patients. PET imaging with 18-kDa translocator protein (TSPO) enables longitudinal monitoring of microglial activation in vivo. Methods: We compiled serial PET measures of TSPO and amyloid with terminal cognitive assessment (water maze) in an AD transgenic mouse model (PS2APP) from 8 to 13 mo of age, followed by immunohistochemical analyses of microglia, amyloid, and synaptic density. Results: Better cognitive outcome and higher synaptic density in PS2APP mice was predicted by higher TSPO expression at 8 mo. The progression of TSPO activation to 13 mo also showed a moderate association with spared cognition, but amyloidosis did not correlate with the cognitive outcome, regardless of the time point. Conclusion: This first PET investigation with longitudinal TSPO and amyloid PET together with terminal cognitive testing in an AD mouse model indicates that continuing microglial response seems to impart preserved cognitive performance.