在Ts65Dn小鼠中模拟阿尔茨海默病相关表型：年龄对Aβ、Tau、pTau、NfL及行为的影响
Modeling Alzheimer's disease related phenotypes in the Ts65Dn mouse: impact of age on Aβ, Tau, pTau, NfL, and behavior.
作者信息
Overk Cassia, Fiorini Emma, Babolin Chiara, Vukicevic Marija, Morici Catherine, Madani Rime, Eligert Valerie, Kosco-Vilbois Marie, Roberts Amanda, Becker Ann, Pfeifer Andrea, Mobley William C
机构信息
Department of Neurosciences, University of California, San Diego, La Jolla, CA, United States.
AC Immune SA, Lausanne, Switzerland.
出版信息
Front Neurosci. 2023 Jun 28;17:1202208. doi: 10.3389/fnins.2023.1202208. eCollection 2023.
INTRODUCTION
People with DS are highly predisposed to Alzheimer's disease (AD) and demonstrate very similar clinical and pathological features. Ts65Dn mice are widely used and serve as the best-characterized animal model of DS.
METHODS
We undertook studies to characterize age-related changes for AD-relevant markers linked to Aβ, Tau, and phospho-Tau, axonal structure, inflammation, and behavior.
RESULTS
We found age related changes in both Ts65Dn and 2N mice. Relative to 2N mice, Ts65Dn mice showed consistent increases in Aβ40, insoluble phospho-Tau, and neurofilament light protein. These changes were correlated with deficits in learning and memory.
DISCUSSION
These data have implications for planning future experiments aimed at preventing disease-related phenotypes and biomarkers. Interventions should be planned to address specific manifestations using treatments and treatment durations adequate to engage targets to prevent the emergence of phenotypes.
引言
唐氏综合征患者极易患阿尔茨海默病（AD），并表现出非常相似的临床和病理特征。Ts65Dn小鼠被广泛使用，是唐氏综合征特征最明确的动物模型。
方法
我们开展了研究，以表征与Aβ、Tau和磷酸化Tau、轴突结构、炎症及行为相关的AD相关标志物的年龄相关变化。
结果
我们在Ts65Dn小鼠和2N小鼠中均发现了年龄相关变化。相对于2N小鼠，Ts65Dn小鼠的Aβ40、不溶性磷酸化Tau和神经丝轻链蛋白持续增加。这些变化与学习和记忆缺陷相关。
讨论
这些数据对于规划未来旨在预防疾病相关表型和生物标志物的实验具有启示意义。应规划干预措施，使用足以作用于靶点的治疗方法和治疗持续时间来应对特定表现，以预防表型的出现。
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