Frontiers in Neuroscience (Jun 2023)

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

  • Cassia Overk,
  • Emma Fiorini,
  • Chiara Babolin,
  • Marija Vukicevic,
  • Catherine Morici,
  • Rime Madani,
  • Valerie Eligert,
  • Marie Kosco-Vilbois,
  • Amanda Roberts,
  • Ann Becker,
  • Andrea Pfeifer,
  • William C. Mobley

DOI
https://doi.org/10.3389/fnins.2023.1202208
Journal volume & issue
Vol. 17

Abstract

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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.MethodsWe undertook 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.

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