Cited by 82Functional Brain Connectivity StudiesAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

Resting State fMRI Reveals Diminished Functional Connectivity in a Mouse Model of Amyloidosis

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Shah, Disha, Jonckers, Elisabeth, Praet, Jelle, Vanhoutte, Greetje, Delgado y Palacios, Rafael, Bigot, Christian, D’Souza, Dany V., Verhoye, Marleen +1 more·2013·PLoS ONE

Abstract

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).”

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  1. [21]Radde R, Bolmont T, Kaeser SA, Coomaraswamy J, Lindau D et al. (2006) Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology. EMBO Rep 7: 940- 946. doi: 10.1038/sj.embor.7400784. PubMed: 16906128. 16906128 PMC1559665 · DOI · Paper page

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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
Published
2013-12-17
Volume
8
Issue
12
Pages
e84241
ISSN
1932-6203 (ISSN-L)
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
Open access
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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