BACKGROUND The aim of this longitudinal study was to assess with positron emission tomography (PET) the relationship between levels of inflammation and the loads of aggregated β-amyloid and tau at baseline and again after 2 years in prodromal Alzheimer's disease. METHODS Forty-three subjects with mild cognitive impairment (MCI) had serial 11C-PK11195 PET over 2 years to measure inflammation changes, and 11C-PiB PET to determine β-amyloid fibril load; 22 also had serial 18F-Flortaucipir PET to determine tau tangle load. Cortical surface statistical mapping was used to localise areas showing significant changes in tracer binding over time and to interrogate correlations between tracer binding of the tracers at baseline and after 2 years. RESULTS Those MCI subjects with high 11C-PiB uptake at baseline (classified as prodromal Alzheimer's disease) had raised inflammation levels which significantly declined across cortical regions over 2 years although their β-amyloid levels continued to rise. Those MCI cases who had low/normal 11C-PiB uptake at baseline but their levels then rose over 2 years were classified as prodromal AD with low Thal phase 1-2 amyloid deposition at baseline. They showed levels of cortical inflammation which correlated with their rising β-amyloid load. Those MCI cases with baseline low 11C-PiB uptake that remained stable were classified as non-AD, and they showed no correlated inflammation levels. Finally, MCI cases which showed both high 11C-PiB and 18F-Flortaucipir uptake at baseline (MCI due to AD) showed a further rise in their tau tangle load over 2 years with a correlated rise in levels of inflammation. CONCLUSIONS Our baseline and 2-year imaging findings are compatible with a biphasic trajectory of inflammation in Alzheimer's disease: MCI cases with low baseline but subsequently rising β-amyloid load show correlated levels of microglial activation which then later decline when the β-amyloid load approaches AD levels. Later, as tau tangles form in β-amyloid positive MCI cases with prodromal AD, the rising tau load is associated with higher levels of inflammation.

中文翻译：

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阿尔茨海默病中神经炎症、β-淀粉样蛋白和 tau 沉积之间的关系：一项纵向 PET 研究。

背景这项纵向研究的目的是通过正电子发射断层扫描 (PET) 评估阿尔茨海默病前驱期炎症水平与基线时和 2 年后聚集的 β-淀粉样蛋白和 tau 蛋白负荷之间的关系。方法 对 43 名患有轻度认知障碍 (MCI) 的受试者进行了 2 年系列 11C-PK11195 PET 测量炎症变化，并使用 11C-PiB PET 确定 β-淀粉样原纤维负荷；22 还具有系列 18F-Flortaucipir PET 以确定 tau 缠结负载。皮层表面统计绘图用于定位显示示踪剂结合随时间显着变化的区域，并询问基线时和 2 年后示踪剂结合之间的相关性。结果 那些基线时 11C-PiB 摄取量较高的 MCI 受试者（被归类为前驱阿尔茨海默氏病）的炎症水平升高，尽管他们的 β-淀粉样蛋白水平持续上升，但在 2 年内，整个皮质区域的炎症水平显着下降。那些基线时 11C-PiB 摄取低/正常但其水平在 2 年内升高的 MCI 病例被归类为基线时 Thal 1-2 期淀粉样蛋白沉积低的前驱 AD。他们表现出皮质炎症水平，这与β-淀粉样蛋白负荷的增加相关。那些基线 11C-PiB 摄取较低且保持稳定的 MCI 病例被归类为非 AD，并且它们没有表现出相关的炎症水平。最后，基线时显示高 11C-PiB 和 18F-Flortaucipir 摄取的 MCI 病例（由于 AD 导致的 MCI）显示其 tau 缠结负荷在 2 年内进一步上升，炎症水平也相应上升。结论 我们的基线和 2 年成像结果与阿尔茨海默氏病炎症的双相轨迹相一致：基线较低但随后 β-淀粉样蛋白负荷上升的 MCI 病例显示小胶质细胞活化水平相关，然后当 β-淀粉样蛋白负荷接近时，小胶质细胞活化水平随后下降AD级别。随后，随着 β-淀粉样蛋白阳性 MCI 伴前驱 AD 病例中 tau 蛋白缠结的形成，tau 蛋白负载的升高与炎症水平升高相关。