Early functional connectivity deficits and progressive microstructural alterations in the TgF344-AD rat model of Alzheimer's Disease: A longitudinal MRI study.

Autor: Anckaerts C; Bio-Imaging Lab, University of Antwerp, Universiteitsplein 1, Wilrijk, Antwerp 2610, Belgium. Electronic address: cynthia.anckaerts@uantwerpen.be., Blockx I; Bio-Imaging Lab, University of Antwerp, Universiteitsplein 1, Wilrijk, Antwerp 2610, Belgium., Summer P; Institute of Experimental Neuroregeneration; Spinal Cord Injury and Tissue Regeneration Centre Salzburg, Paracelsus Medical University, Strubergasse 22, Salzburg 5020, Austria., Michael J; Institute of Experimental Neuroregeneration; Spinal Cord Injury and Tissue Regeneration Centre Salzburg, Paracelsus Medical University, Strubergasse 22, Salzburg 5020, Austria; Institute of Molecular Regenerative Medicine; Spinal Cord Injury and Tissue Regeneration Centre Salzburg, Paracelsus Medical University, Strubergasse 22, Salzburg 5020, Austria., Hamaide J; Bio-Imaging Lab, University of Antwerp, Universiteitsplein 1, Wilrijk, Antwerp 2610, Belgium., Kreutzer C; Institute of Experimental Neuroregeneration; Spinal Cord Injury and Tissue Regeneration Centre Salzburg, Paracelsus Medical University, Strubergasse 22, Salzburg 5020, Austria., Boutin H; Wolfson Molecular Imaging Centre, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester M20 3LJ, UK., Couillard-Després S; Institute of Experimental Neuroregeneration; Spinal Cord Injury and Tissue Regeneration Centre Salzburg, Paracelsus Medical University, Strubergasse 22, Salzburg 5020, Austria., Verhoye M; Bio-Imaging Lab, University of Antwerp, Universiteitsplein 1, Wilrijk, Antwerp 2610, Belgium., Van der Linden A; Bio-Imaging Lab, University of Antwerp, Universiteitsplein 1, Wilrijk, Antwerp 2610, Belgium.
Jazyk: angličtina
Zdroj: Neurobiology of disease [Neurobiol Dis] 2019 Apr; Vol. 124, pp. 93-107. Date of Electronic Publication: 2018 Nov 13.
DOI: 10.1016/j.nbd.2018.11.010
Abstrakt: The development and characterization of new improved animal models is pivotal in Alzheimer's Disease (AD) research, since valid models enable the identification of early pathological processes, which are often not accessible in patients, as well as subsequent target discovery and evaluation. The TgF344-AD rat model of AD, bearing mutant human amyloid precursor protein (APPswe) and Presenilin 1 (PSEN1ΔE9) genes, has been described to manifest the full spectrum of AD pathology similar to human AD, i.e. progressive cerebral amyloidosis, tauopathy, neuronal loss and age-dependent cognitive decline. Here, AD-related pathology in female TgF344-AD rats was examined longitudinally between 6 and 18 months by means of complementary translational MRI techniques: resting state functional MRI (rsfMRI) to evaluate functional connectivity (FC) and diffusion tensor imaging (DTI) to assess the microstructural integrity. Additionally, an evaluation of macroscopic changes (3D anatomical MRI) and an image-guided validation of ex vivo pathology were performed. We identified slightly decreased FC at 6 months followed by severe and widespread hypoconnectivity at 10 months of age as the earliest detectable pathological MRI hallmark. This initial effect was followed by age-dependent progressive microstructural deficits in parallel with age-dependent ex vivo AD pathology, without signs of macroscopic alterations such as hippocampal atrophy. This longitudinal MRI study in the TgF344-AD rat model of AD revealed early rsfMRI and DTI abnormalities as seen in human AD patients. The characterization of AD pathology in this rat model using non-invasive MRI techniques further highlights the translational value of this model, as well as its use for potential treatment evaluation.
(Copyright © 2018. Published by Elsevier Inc.)
Databáze: MEDLINE
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