Publication
Title
Early functional connectivity deficits and progressive microstructural alterations in the TgF344-AD rat model of Alzheimers disease : a longitudinal MRI study
Author
Abstract
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.
Language
English
Source (journal)
Neurobiology of disease. - San Diego, Calif.
Publication
San Diego, Calif. : 2019
ISSN
0969-9961
Volume/pages
124 (2019) , p. 93-107
ISI
000459217800009
Pubmed ID
30445024
Full text (Publisher's DOI)
Full text (open access)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Project info
Imaging of Neuroinflammation in Neurodegenerative Diseases (INMIND).
Amyloid β and sleep problems, a neurotoxic pas de deux during aging?
Neuro Image-guided decoding of mechanisms involved in healthy, accelerated and pathological aging.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 10.12.2018
Last edited 11.09.2021
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