title: Resting state FMRI reveals diminished functional connectivity in a mouse model of amyloidosis.
abstract: BACKGROUND
  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.
authors.affiliation: Bio-Imaging Laboratory, University of Antwerp, Antwerp, Belgium.
authors.forename: Disha
authors.initials: D
authors.lastname: Shah
authors.affiliation: Bio-Imaging Laboratory, University of Antwerp, Antwerp, Belgium.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Jonckers
authors.affiliation: Bio-Imaging Laboratory, University of Antwerp, Antwerp, Belgium.
authors.forename: Jelle
authors.initials: J
authors.lastname: Praet
authors.affiliation: Bio-Imaging Laboratory, University of Antwerp, Antwerp, Belgium.
authors.forename: Greetje
authors.initials: G
authors.lastname: Vanhoutte
authors.affiliation: Bio-Imaging Laboratory, University of Antwerp, Antwerp, Belgium.
authors.forename: Rafael
authors.initials: R
authors.lastname: Delgado Y Palacios
authors.affiliation: Bio-Imaging Laboratory, University of Antwerp, Antwerp, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Bigot
authors.affiliation: Bio-Imaging Laboratory, University of Antwerp, Antwerp, Belgium ; F. Hoffmann-La Roche Pharmaceuticals Ltd, Neuroscience Discovery, Basel, Switzerland.
authors.forename: Dany V
authors.initials: DV
authors.lastname: D'Souza
authors.affiliation: Bio-Imaging Laboratory, University of Antwerp, Antwerp, Belgium.
authors.forename: Marleen
authors.initials: M
authors.lastname: Verhoye
authors.affiliation: Bio-Imaging Laboratory, University of Antwerp, Antwerp, Belgium.
authors.forename: Annemie
authors.initials: A
authors.lastname: Van der Linden
mesh_terms: D000686:Amyloidosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice