Early-in-life neuroanatomical and behavioural trajectories in a triple transgenic model of Alzheimer’s disease
Abstract
Animal models of Alzheimer's disease (AD) can be used to determine the progressive neurodegeneration characteristics of AD in vivo using magnetic resonance imaging (MRI). Given the need for therapeutic interventions before the onset of frank AD, it is critical to examine if AD models demonstrate neuroanatomical remodeling in an equivalent preclinical phase. This manuscript examines the trajectories of brain and behavioural changes in the Triple transgenic mouse model (3xTg) prior to the development of AD-like behaviours. The 3xTg mimics both β-amyloid plaques and neurofibrillary tangles through three mutations associated with familial AD, namely: PS1 M146V , APP Swe , and tau P301L transgenes. We performed detailed investigation using longitudinal structural MRI at 6, 8, 12, 16, 20, and 24 weeks old to assess neuroanatomical changes using volumetric and deformation-based analyses. Learning- and memory-related behaviour were assessed through the Morris water maze at 9, 17, and 25 weeks of age. There was the absence of major memory deficits with the notable exception of water maze conducted at 17 weeks old, where 3xTg group spent significantly less time in the quadrant of interest in the probe trial. Through volumetric and deformation-based analyses, we observed relative decrease over time in the 3xTg group in the third ventricle, piriform cortex, fornix, and fimbria relative to the control group. We also observed decreases over time in the control mice in the hippocampus, ento…
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Brain-wide volume measurements have yielded inconsistent results in the 3×Tg-AD model, with some studies reporting volumetric changes and others finding no significant differences.
“Although most studies have reported volumetric changes throughout various brain regions over time (including both decreases and increases) (Kong et al., 2018; Chiquita et al., 2019; Rollins et al., 2019; Güell-Bosch et al., 2020), others have found no significant differences in brain volume between 3×Tg-AD mice and controls (Kastyak-Ibrahim et al., 2013; Wu et al., 2015; Montoliu-Gaya et al., 2018”
From Multimodal MRI combined with RNA sequencing reveals pathological signatures in the 9-month-old 3×Tg-AD mouse brain (2026) · cites this paper as Kong et al., 2018
Longitudinal studies have revealed significant changes in brain volumes (both increases and decreases) in 3×Tg-AD mice during the early stages from 1.5 months to 6 months of age.
“Longitudinal studies have revealed significant changes in brain volumes (both increases and decreases) in 3×Tg-AD mice during the early stages from 1.5 months to 6 months of age (Kong et al., 2018; Rollins et al., 2019).”
From Multimodal MRI combined with RNA sequencing reveals pathological signatures in the 9-month-old 3×Tg-AD mouse brain (2026) · cites this paper as Kong et al., 2018
Previous studies on 3×Tg-AD mice have reported significant volumetric decreases and WM microstructural abnormalities in the corpus callosum and internal capsule compared with controls.
“Previous studies on 3×Tg-AD mice have reported significant volumetric decreases (Kong et al., 2018) and WM microstructural abnormalities (Praet et al., 2018; Gatto et al., 2019; Bergamino et al., 2023) in the CC and internal capsule compared with controls.”
From Multimodal MRI combined with RNA sequencing reveals pathological signatures in the 9-month-old 3×Tg-AD mouse brain (2026) · cites this paper as Kong et al., 2018
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Diffusion MRI detects early brain microstructure abnormalities in 2-month-old 3×Tg-AD mice
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- Authors
- Kong, V., Devenyi, G. A., Gallino, D., Ayranci, G., Germann, J., Rollins, C., & Chakravarty, M. M.
- Affiliations
- Douglas Mental Health University Institute (CA)
- Corresponding author
- Chakravarty, M. Mallar
- Venue
- Brain Structure and Function
- Published
- 2018-06-13
- Volume
- 223
- Issue
- 7
- Pages
- 3365-3382
- ISSN
- 1863-2653 (ISSN-L)
- 1863-2661
- OpenAlex
- W2808452326
- Cited by
- 32
- References
- 8
- Citations by year
- 2026: 3 · 2025: 5 · 2023: 3 · 2022: 6 · 2021: 9 · 2020: 2 · 2019: 3 · 2018: 1
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Brain Structure and Function (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fondation Brain Canada
- CIHR
- NSERC
- Weston Brain Institute
- FQRNT
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, triple transgenic mouse model, 3xTg-AD mice, preclinical neurodegeneration, brain volume changes, deformation-based morphometry, spatial memory impairment, Morris water maze, amyloid plaques, tau pathology, neurodevelopmental delay, hippocampus, piriform cortex, fornix, fimbria, longitudinal structural MRI
- MeSH terms
- Age Factors, Alzheimer Disease, Animals, Behavior, Animal, Brain, Female, Learning, Magnetic Resonance Imaging, Male, Memory, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Phenotype, Time Factors, Amyloid beta-Protein Precursor, Neurofibrillary Tangles, tau Proteins, Maze Learning, Genetic Predisposition to Disease, Presenilin-1, Mice, 129 Strain, Plaque, Amyloid
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