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Front. Aging Neurosci. | doi: 10.3389/fnagi.2019.00039

Neuroimaging the 3xTg Alzheimer’s disease mouse model reveals white matter alterations alongside decreased functional connectivity

  • 1City University of Hong Kong, Hong Kong
  • 2Instituto de Neurobiología, National Autonomous University of Mexico, Mexico

Alzheimer’s disease is characterized by amyloid-β plaques and neurofibrillary tangles. The 3xTg mouse model of Alzheimer’s disease progressively develops plaques and tangles, recapitulating the neuropathology of human Alzheimer’s disease. We investigated the 3xTg mouse model using diffusion tensor imaging, resting-state functional magnetic resonance imaging, and volumetry at 2 months of age prior to the development of intraneuronal plaque accumulation. The 3xTg had significant fractional anisotropy increase and radial diffusivity decrease in the cortex compared with wild-type controls, while axial diffusivity and mean diffusivity were similar. Ventricular volume in the 3xTg was four times larger compared with that of controls. Interhemispheric hippocampal connectivity was decreased in the 3xTg while connectivity in the caudate putamen was similar. This study provided valuable neuroimaging characterization of the 3xTg model at an early stage of Alzheimer’s disease progression. The results are important for translating animal research to humans.

Keywords: Alzheimer’s disease (AD), 3xTg mouse model, Diffusion tensor imaging (DTI), Resting-state functional magnetic resonance imaging (rsfMRI), fractional anisotropy, connectivity, radial diffusivity

Received: 21 Aug 2018; Accepted: 08 Feb 2019.

Edited by:

Hanting Zhang, West Virginia University, United States

Reviewed by:

Lydia Gimenez-Llort, Institute of Neurosciences, Autonomous University of Barcelona, Spain
Bjorn Johansson, Karolinska Institute (KI), Sweden
Manuel Desco, Hospital General Universitario Gregorio Marañón, Spain  

Copyright: © 2019 Manno, Hernandez Cortes-Manno, Ahmed, Cheng, Barrios and Lau. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Francis A. Manno, City University of Hong Kong, Kowloon, Hong Kong, francis.manno@nyu.edu