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

• Published in: Frontiers in neuroscience Vol. 17; p. 1202208
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 28.06.2023; Frontiers Media S.A
• Subjects: Age; Alzheimer's disease; animal model; Animal models; Behavior; Biomarkers; Dementia; Down syndrome; DS-AD; Laboratory animals; Neurodegenerative diseases; Neuropathology; Neuroscience; Pathogenesis; Phenotypes; Proteins; tau; Tau protein; Abeta; Alzheimer’s disease; DS-AD; tau; Down syndrome; animal model; behavior; age
• ISSN: 1662-453X; 1662-4548; 1662-453X
• DOI: 10.3389/fnins.2023.1202208

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. We undertook studies to characterize age-related changes for AD-relevant markers linked to Aβ, Tau, and phospho-Tau, axonal structure, inflammation, and behavior. 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. 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.