Abstract：
Nearly two-thirds of patients diagnosed with Alzheimer\'s disease (AD) are female. In addition, female patients with AD have more significant cognitive impairment than males at the same disease stage. This disparity suggests there are sex differences in AD progression. While females appear to be more affected by AD, most published behavioral studies utilize male mice. In humans, there is an association between antecedent attention-deficit/hyperactivity disorder and increased risk of dementia. Functional connectivity studies indicate that dysfunctional cortico-striatal networks contribute to hyperactivity in attention deficit hyperactivity disorder. Higher plaque density in the striatum accurately predicts the presence of clinical AD pathology. In addition, there is a link between AD-related memory dysfunction and dysfunctional dopamine signaling.
With the need to consider sex as a biological variable, we investigated the influence of sex on striatal plaque burden, dopaminergic signaling, and behavior in prodromal 5XFAD mice.
Six-month-old male and female 5XFAD and C57BL/6J mice were evaluated for striatal amyloid plaque burden, locomotive behavior, and changes in dopaminergic machinery in the striatum.
5XFAD female mice had a higher striatal amyloid plaque burden than male 5XFAD mice. 5XFAD females, but not males, were hyperactive. Hyperactivity in female 5XFAD mice was associated with increased striatal plaque burden and changes in dopamine signaling in the dorsal striatum.
Our results indicate that the progression of amyloidosis involves the striatum in females to a greater extent than in males. These studies have significant implications for using male-only cohorts in the study of AD progression.
With the need to consider sex as a biological variable, we investigated the influence of sex on striatal plaque burden, dopaminergic signaling, and behavior in prodromal 5XFAD mice.
Six-month-old male and female 5XFAD and C57BL/6J mice were evaluated for striatal amyloid plaque burden, locomotive behavior, and changes in dopaminergic machinery in the striatum.
5XFAD female mice had a higher striatal amyloid plaque burden than male 5XFAD mice. 5XFAD females, but not males, were hyperactive. Hyperactivity in female 5XFAD mice was associated with increased striatal plaque burden and changes in dopamine signaling in the dorsal striatum.
Our results indicate that the progression of amyloidosis involves the striatum in females to a greater extent than in males. These studies have significant implications for using male-only cohorts in the study of AD progression.
摘要：
背景：诊断为阿尔茨海默病（AD）的患者中，近三分之二是女性。此外,在同一疾病阶段，女性AD患者的认知障碍比男性更明显。这种差异表明在AD进展中存在性别差异。虽然女性似乎更容易受到AD的影响，大多数已发表的行为研究利用雄性小鼠。在人类中,先前的注意力缺陷/多动障碍与痴呆风险增加之间存在关联.功能连接研究表明，皮质纹状体网络功能失调有助于注意缺陷多动障碍的多动。纹状体中较高的斑块密度准确地预测了临床AD病理的存在。此外,与AD相关的记忆功能障碍和功能失调的多巴胺信号之间存在联系。
目标：需要将性别视为生物学变量，我们调查了性别对纹状体斑块负荷的影响，多巴胺能信号，和前驱5XFAD小鼠的行为。
方法：对6个月大的雄性和雌性5XFAD和C57BL/6J小鼠进行纹状体淀粉样斑块负荷评估，机车行为，纹状体多巴胺能机制的变化。
结果：5XFAD雌性小鼠的纹状体淀粉样蛋白斑块负荷高于雄性5XFAD小鼠。5XFAD女性，但不是男性，过度活跃。雌性5XFAD小鼠的过度活跃与纹状体斑块负荷增加和背侧纹状体中多巴胺信号传导的变化有关。
结论：我们的结果表明，女性淀粉样变性的进展涉及纹状体的程度大于男性。这些研究对于在AD进展研究中使用仅男性队列具有重要意义。
目标：需要将性别视为生物学变量，我们调查了性别对纹状体斑块负荷的影响，多巴胺能信号，和前驱5XFAD小鼠的行为。
方法：对6个月大的雄性和雌性5XFAD和C57BL/6J小鼠进行纹状体淀粉样斑块负荷评估，机车行为，纹状体多巴胺能机制的变化。
结果：5XFAD雌性小鼠的纹状体淀粉样蛋白斑块负荷高于雄性5XFAD小鼠。5XFAD女性，但不是男性，过度活跃。雌性5XFAD小鼠的过度活跃与纹状体斑块负荷增加和背侧纹状体中多巴胺信号传导的变化有关。
结论：我们的结果表明，女性淀粉样变性的进展涉及纹状体的程度大于男性。这些研究对于在AD进展研究中使用仅男性队列具有重要意义。
