Modeling Alzheimer’s disease related phenotypes in the Ts65Dn mouse: impact of age on Aβ, Tau, pTau, NfL, and behavior

Frontiers in Neuroscience

Neuroscience

Catherine Morici¹  Valerie Eligert¹  Marie Kosco-Vilbois¹  Chiara Babolin¹  Andrea Pfeifer¹  Emma Fiorini¹  Marija Vukicevic¹  Rime Madani¹  Amanda Roberts²  Ann Becker³  Cassia Overk³  William C. Mobley³ 

[1] AC Immune SA, Lausanne, Switzerland;Animal Models Core Facility, The Scripps Research Institute, La Jolla, CA, United States;Department of Neurosciences, University of California, San Diego, La Jolla, CA, United States;

关键词: DS-AD;    animal model;    age;    Down syndrome;    Alzheimer’s disease;    tau;    Abeta;    behavior;   

DOI  :  10.3389/fnins.2023.1202208

 received in 2023-04-07, accepted in 2023-05-31,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionPeople 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.MethodsWeundertook studies to characterize age-related changes for AD-relevant markers linked to Aβ, Tau, and phospho-Tau, axonal structure, inflammation, and behavior.ResultsWe 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.DiscussionThese 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.

【 授权许可】

Unknown   
Copyright © 2023 Overk, Fiorini, Babolin, Vukicevic, Morici, Madani, Eligert, Kosco-Vilbois, Roberts, Becker, Pfeifer and Mobley.