关键词: ApoE mouse model DNA aptamer MRI contrast agent oligomeric amyloid-beta tau mouse model time-dependent signal enhancement

来  源:   DOI:10.3389/fphar.2024.1392729   PDF(Pubmed)

Abstract:
UNASSIGNED: Oligomeric amyloid beta (oAβ) is a toxic factor that acts in the early stage of Alzheimer\'s disease (AD) and may initiate the pathologic cascade. Therefore, detecting oAβ has a crucial role in the early diagnosis, monitoring, and treatment of AD.
UNASSIGNED: The purpose of this study was to evaluate MRI signal changes in different mouse models and the time-dependent signal changes using our novel gadolinium (Gd)-dodecane tetraacetic acid (DOTA)- ob5 aptamer contrast agent.
UNASSIGNED: We developed an MRI contrast agent by conjugating Gd-DOTA-DNA aptamer called ob5 to evaluate its ability to detect oAβ deposits in the brain using MRI. A total of 10 control mice, 9 3xTg AD mice, and 11 APP/PS/Tau AD mice were included in this study, with the age of each model being 16 or 36 weeks. A T1-weighted image was acquired at the time points before (0 min) and after injection of the contrast agent at 5, 10, 15, 20, and 25 min. The analyses were performed to compare MRI signal differences among the three groups and the time-dependent signal differences in different mouse models.
UNASSIGNED: Both 3xTg AD and APP/PS/Tau AD mouse models had higher signal enhancement than control mice at all scan-time points after injection of our contrast media, especially in bilateral hippocampal areas. In particular, all Tg AD mouse models aged 16 weeks showed a higher contrast enhancement than those aged 36 weeks. For 3xTg AD and APP/PS/Tau AD groups, the signal enhancement was significantly different among the five time points (0 min, 5 min, 10 min, 15 min, 20 min, and 25 min) in multiple ROI areas, typically in the bilateral hippocampus, left thalamus, and left amygdala.
UNASSIGNED: The findings of this study suggest that the expression of the contrast agent in different AD models demonstrates its translational flexibility across different species. The signal enhancement peaked around 15-20 min after injection of the contrast agent. Therefore, our novel contrast agent targeting oAβ has the potential ability to diagnose early AD and monitor the progression of AD.
摘要:
寡聚淀粉样β(oAβ)是一种毒性因子,在阿尔茨海默病(AD)的早期起作用,并可能引发病理级联反应。因此,检测oAβ在早期诊断中起着至关重要的作用,监测,和AD的治疗。
这项研究的目的是使用我们的新型钆(Gd)-十二烷四乙酸(DOTA)-ob5适体造影剂评估不同小鼠模型中的MRI信号变化和时间依赖性信号变化。
我们通过缀合称为ob5的Gd-DOTA-DNA适体开发了一种MRI造影剂,以评估其使用MRI检测脑中oAβ沉积物的能力。共10只对照小鼠,9只3xTgAD小鼠,本研究包括11只APP/PS/TauAD小鼠,每个模型的年龄为16或36周。在注射造影剂之前(0分钟)和之后5、10、15、20和25分钟的时间点获取T1加权图像。进行分析以比较三组之间的MRI信号差异以及不同小鼠模型中的时间依赖性信号差异。
3xTgAD和APP/PS/TauAD小鼠模型在注射我们的造影剂后的所有扫描时间点均比对照小鼠具有更高的信号增强,尤其是在双侧海马区。特别是,所有16周龄的TgAD小鼠模型的对比度增强均高于36周龄的模型。对于3xTgAD和APP/PS/TauAD组,信号增强在五个时间点(0分钟,5分钟,10分钟,15分钟,20分钟,和25分钟)在多个ROI区域,通常在双侧海马,左丘脑,离开杏仁核.
这项研究的结果表明,造影剂在不同AD模型中的表达证明了其在不同物种之间的翻译灵活性。注射造影剂后约15-20分钟,信号增强达到峰值。因此,我们靶向oAβ的新型造影剂具有诊断早期AD和监测AD进展的潜在能力。
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