Abstract：
BACKGROUND: Reactive astrocytes play an important role in the development of Alzheimer\'s disease and primary tauopathies. Here, we aimed to investigate the relationships between reactive astrocytes. Microgliosis and glucose metabolism with Tau and amyloid beta pathology by using multi-tracer imaging in widely used tauopathy and familial Alzheimer\'s disease mouse models.
RESULTS: Positron emission tomography imaging using [18F]PM-PBB3 (tau), [18F]florbetapir (amyloid-beta), [18F]SMBT-1 (monoamine oxidase-B), [18F]DPA-714 (translocator protein) and [18F]fluorodeoxyglucose was carried out in 3- and 7-month-old rTg4510 tau mice, 5 × FAD familial Alzheimer\'s disease mice and wild-type mice. Immunofluorescence staining was performed to validate the pathological distribution in the mouse brain after in vivo imaging. We found increased regional levels of [18F]PM-PBB3, [18F]SMBT-1, and [18F]DPA-714 and hypoglucose metabolism in the brains of 7-month-old rTg4510 mice compared to age-matched wild-type mice. Increased [18F]SMBT-1 uptake was observed in the brains of 3, 7-month-old 5 × FAD mice, with elevated regional [18F]florbetapir and [18F]DPA-714 uptakes in the brains of 7-month-old 5 × FAD mice, compared to age-matched wild-type mice. Positive correlations were shown between [18F]SMBT-1 and [18F]PM-PBB3, [18F]DPA-714 and [18F]PM-PBB3 in rTg4510 mice, and between [18F]florbetapir and [18F]DPA-714 SUVRs in 5 × FAD mice.
CONCLUSIONS: In summary, these findings provide in vivo evidence that reactive astrocytes, microglial activation, and cerebral hypoglucose metabolism are associated with tau and amyloid pathology development in animal models of tauopathy and familial Alzheimer\'s disease.
RESULTS: Positron emission tomography imaging using [18F]PM-PBB3 (tau), [18F]florbetapir (amyloid-beta), [18F]SMBT-1 (monoamine oxidase-B), [18F]DPA-714 (translocator protein) and [18F]fluorodeoxyglucose was carried out in 3- and 7-month-old rTg4510 tau mice, 5 × FAD familial Alzheimer\'s disease mice and wild-type mice. Immunofluorescence staining was performed to validate the pathological distribution in the mouse brain after in vivo imaging. We found increased regional levels of [18F]PM-PBB3, [18F]SMBT-1, and [18F]DPA-714 and hypoglucose metabolism in the brains of 7-month-old rTg4510 mice compared to age-matched wild-type mice. Increased [18F]SMBT-1 uptake was observed in the brains of 3, 7-month-old 5 × FAD mice, with elevated regional [18F]florbetapir and [18F]DPA-714 uptakes in the brains of 7-month-old 5 × FAD mice, compared to age-matched wild-type mice. Positive correlations were shown between [18F]SMBT-1 and [18F]PM-PBB3, [18F]DPA-714 and [18F]PM-PBB3 in rTg4510 mice, and between [18F]florbetapir and [18F]DPA-714 SUVRs in 5 × FAD mice.
CONCLUSIONS: In summary, these findings provide in vivo evidence that reactive astrocytes, microglial activation, and cerebral hypoglucose metabolism are associated with tau and amyloid pathology development in animal models of tauopathy and familial Alzheimer\'s disease.
摘要：
背景：反应性星形胶质细胞在阿尔茨海默病和原发性tau蛋白病的发生发展中起重要作用。这里,我们的目的是研究反应性星形胶质细胞之间的关系。通过在广泛使用的tau蛋白病和家族性阿尔茨海默病小鼠模型中使用多示踪剂成像，小胶质细胞增生和糖代谢与Tau和淀粉样β病理有关。
结果：使用[18F]PM-PBB3（tau）的正电子发射断层扫描成像，[18F]florbetapir(淀粉样蛋白-β)，[18F]SMBT-1（单胺氧化酶-B），在3个月和7个月大的rTg4510tau小鼠中进行[18F]DPA-714（转运蛋白）和[18F]氟脱氧葡萄糖，5×FAD家族性阿尔茨海默病小鼠和野生型小鼠。进行免疫荧光染色以验证体内成像后小鼠脑中的病理分布。我们发现与年龄匹配的野生型小鼠相比，7月龄rTg4510小鼠的大脑中[18F]PM-PBB3，[18F]SMBT-1和[18F]DPA-714的区域水平增加。在3，7个月大的5×FAD小鼠的大脑中观察到[18F]SMBT-1摄取增加，在7个月大的5×FAD小鼠的大脑中增加了区域[18F]florbetapir和[18F]DPA-714的摄取，与年龄匹配的野生型小鼠相比。rTg4510小鼠的[18F]SMBT-1与[18F]PM-PBB3、[18F]DPA-714与[18F]PM-PBB3呈正相关,在5×FAD小鼠中，[18F]florbetapir和[18F]DPA-714SUVR之间。
结论：总之，这些发现提供了体内证据，表明反应性星形胶质细胞，小胶质细胞激活，在Tau蛋白病和家族性阿尔茨海默病的动物模型中,脑低糖代谢与tau蛋白和淀粉样蛋白病理发育有关。
结果：使用[18F]PM-PBB3（tau）的正电子发射断层扫描成像，[18F]florbetapir(淀粉样蛋白-β)，[18F]SMBT-1（单胺氧化酶-B），在3个月和7个月大的rTg4510tau小鼠中进行[18F]DPA-714（转运蛋白）和[18F]氟脱氧葡萄糖，5×FAD家族性阿尔茨海默病小鼠和野生型小鼠。进行免疫荧光染色以验证体内成像后小鼠脑中的病理分布。我们发现与年龄匹配的野生型小鼠相比，7月龄rTg4510小鼠的大脑中[18F]PM-PBB3，[18F]SMBT-1和[18F]DPA-714的区域水平增加。在3，7个月大的5×FAD小鼠的大脑中观察到[18F]SMBT-1摄取增加，在7个月大的5×FAD小鼠的大脑中增加了区域[18F]florbetapir和[18F]DPA-714的摄取，与年龄匹配的野生型小鼠相比。rTg4510小鼠的[18F]SMBT-1与[18F]PM-PBB3、[18F]DPA-714与[18F]PM-PBB3呈正相关,在5×FAD小鼠中，[18F]florbetapir和[18F]DPA-714SUVR之间。
结论：总之，这些发现提供了体内证据，表明反应性星形胶质细胞，小胶质细胞激活，在Tau蛋白病和家族性阿尔茨海默病的动物模型中,脑低糖代谢与tau蛋白和淀粉样蛋白病理发育有关。
