Resting State fMRI Reveals Diminished Functional Connectivity in a Mouse Model of Amyloidosis
Open accessAbstract
INTRODUCTION: Functional connectivity (FC) studies have gained immense popularity in the evaluation of several neurological disorders, such as Alzheimer's disease (AD). AD is a complex disorder, characterised by several pathological features. The problem with FC studies in patients is that it is not straightforward to focus on a specific aspect of pathology. In the current study, resting state functional magnetic resonance imaging (rsfMRI) is applied in a mouse model of amyloidosis to assess the effects of amyloid pathology on FC in the mouse brain. METHODS: Nine APP/PS1 transgenic and nine wild-type mice (average age 18.9 months) were imaged on a 7T MRI system. The mice were anesthetized with medetomidine and rsfMRI data were acquired using a gradient echo EPI sequence. The data were analysed using a whole brain seed correlation analysis and interhemispheric FC was evaluated using a pairwise seed analysis. Qualitative histological analyses were performed to assess amyloid pathology, inflammation and synaptic deficits. RESULTS: The whole brain seed analysis revealed an overall decrease in FC in the brains of transgenic mice compared to wild-type mice. The results showed that interhemispheric FC was relatively preserved in the motor cortex of the transgenic mice, but decreased in the somatosensory cortex and the hippocampus when compared to the wild-type mice. The pairwise seed analysis confirmed these results. Histological analyses confirmed the presence of amyloid pathology, inflammation and synaptic deficits in the transgenic mice. CONCLUSIONS: In the current study, rsfMRI demonstrated decreased FC in APP/PS1 transgenic mice compared to wild-type mice in several brain regions. The APP/PS1 transgenic mice had advanced amyloid pathology across the brain, as well as inflammation and synaptic deficits surrounding the amyloid plaques. Future studies should longitudinally evaluate APP/PS1 transgenic mice and correlate the rsfMRI findings to specific stages of amyloid pathology.
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Previous studies of APP/PS1 and ArcBeta transgenic mice have demonstrated deficits in the functional connectivity of multiple brain regions that is associated with amyloid deposition.
“Previous studies of APP/PS1 and ArcBeta transgenic mice have demonstrated deficits in the functional connectivity of multiple brain regions that is associated with amyloid deposition (Bero et al., 2012; Grandjean et al., 2014; Shah et al., 2013).”
From Functional and structural connectome properties in the 5XFAD transgenic mouse model of Alzheimer’s disease (2018) · cites this paper as Shah et al., 2013
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Self-citationDental Stem Cells in Oral, Maxillofacial and Craniofacial Regeneration
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Self-citationReduced Prefrontal-Thalamic Theta Flow During Working Memory Retrieval in APP/PS1 Mice
Zhang, S., Ai, H., Wang, J., Liu, T., Zheng, X., Tian, X., & Bai, W. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-231078 · Cited by 3 · see citing works
Preserved functional networks in a hydrocephalic mouse
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Correspondence of large-scale functional brain network decline across aging mice and humans
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Disrupted structural connectivity in ArcAβ mouse model of Aβ amyloidosis
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“…functional network and compromised WM indices have shown in TgF344 rats (Anckaerts et al., 2019), 5XFAD mice (Kesler et al., 2018), APP/PS1 mice (Shah et al., 2013, Bero et al., 2012), ArcAβ mice (Grandjean et al., 2014, Grandjean et al., 2016), aging apoE4 and apoE-KO mice (Zerbi et al., 2014)…”
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Self-citationImaging biomarkers in neurodegenerative diseases: advances and challenges
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Aging-Dependent Loss of Connectivity in Alzheimer’s Model Mice with Rescue by mGluR5 ModulatorPreprint
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The lateral entorhinal cortex is a hub for local and global dysfunction in pre-tauopathy statesPreprint
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MRI analysis of brain connectivity in a mouse model of Alzheimer’s disease
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Isolation housing exacerbates Alzheimer’s Disease phenotype in aged APP KI micePreprint
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Experimental Models of Brain Disease: MRI Studies
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- Authors
- Shah, D., Jonckers, E., Praet, J., Vanhoutte, G., Delgado y Palacios, R., Bigot, C., D’Souza, D. V., Verhoye, M., & Van der Linden, A.
- Affiliations
- University of Antwerp (BE)
- Corresponding author
- Jonckers, Elisabeth
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-12-17
- Volume
- 8
- Issue
- 12
- Pages
- e84241
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3866274
- OpenAlex
- W2085689917
- Cited by
- 82
- References
- 36
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 3 · 2023: 8 · 2022: 7 · 2021: 2 · 2020: 5 · 2019: 11 · 2018: 12 · 2017: 6 · 2016: 4 · 2015: 7 · 2014: 5 · 2013: 1
- FWCI
- 3.10
- Type
- journal article
- Language
- en
- Update notices
- correction (2014-01-10)
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- European Commission (212043, 2007–2013, FP7 2007-2013, FP7/2007, 278850)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- resting-state functional connectivity, amyloidosis, APP/PS1 mice, Alzheimer's disease, amyloid plaques, interhemispheric connectivity, hippocampus, somatosensory cortex, motor cortex, neuroinflammation, synaptic deficits, mouse model
- MeSH terms
- Amyloidosis, Animals, Brain, Brain Mapping, Cerebral Cortex, Disease Models, Animal, Magnetic Resonance Imaging, Male, Mice
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