Early brain connectivity alterations and cognitive impairment in a rat model of Alzheimer’s disease

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• dc.contributor.author Muñoz-Moreno, Emma
• dc.contributor.author Tudela, Raúl
• dc.contributor.author López-Gil, Xavier
• dc.contributor.author Soria Rodríguez, Guadalupe
• dc.date.accessioned 2022-10-04T06:14:20Z
• dc.date.available 2022-10-04T06:14:20Z
• dc.date.issued 2018
• dc.description Supplemental material file: Cognitive training description and evaluation
• dc.description.abstract Animal models of Alzheimer’s disease (AD) are essential to understanding the disease progression and to development of early biomarkers. Because AD has been described as a disconnection syndrome, magnetic resonance imaging (MRI)-based connectomics provides a highly translational approach to characterizing the disruption in connectivity associated with the disease. In this study, a transgenic rat model of AD (TgF344-AD) was analyzed to describe both cognitive performance and brain connectivity at an early stage (5 months of age) before a significant concentration of β-amyloid plaques is present. Cognitive abilities were assessed by a delayed nonmatch-to-sample (DNMS) task preceded by a training phase where the animals learned the task. The number of training sessions required to achieve a learning criterion was recorded and evaluated. After DNMS, MRI acquisition was performed, including diffusion-weighted MRI and resting-state functional MRI, which were processed to obtain the structural and functional connectomes, respectively. Global and regional graph metrics were computed to evaluate network organization in both transgenic and control rats. The results pointed to a delay in learning the working memory-related task in the AD rats, which also completed a lower number of trials in the DNMS task. Regarding connectivity properties, less efficient organization of the structural brain networks of the transgenic rats with respect to controls was observed. Specific regional differences in connectivity were identified in both structural and functional networks. In addition, a strong correlation was observed between cognitive performance and brain networks, including whole-brain structural connectivity as well as functional and structural network metrics of regions related to memory and reward processes. In this study, connectivity and neurocognitive impairments were identified in TgF344-AD rats at a very early stage of the disease when most of the pathological hallmarks have not yet been detected. Structural and functional network metrics of regions related to reward, memory, and sensory performance were strongly correlated with the cognitive outcome. The use of animal models is essential for the early identification of these alterations and can contribute to the development of early biomarkers of the disease based on MRI connectomics.
• dc.description.sponsorship This work was funded by the PI14/00595 project, which is integrated into the Plan Nacional I + D + I and cofunded by Instituto de Salud Carlos (ISCIII), Subdirección General de Evaluación, and the European Regional Development Fund (ERDF). It was also funded by the Fundació La Marató de TV3 (201441 10). Consorcio Centro de Investigación Biomédica en Red (CIBER) de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) is an initiative financed by ISCIII with assistance from the ERDF. The work was also funded by InMind project financed by the European Community (FP7-HEALTH-2011.2.2.1-2, nº 278850). TgF344-AD rats were obtain through the InMind Consortium following kind donation by Dr. T Town.
• dc.format.mimetype application/pdf
• dc.identifier.citation Muñoz-Moreno E, Tudela R, López-Gil X, Soria G. Early brain connectivity alterations and cognitive impairment in a rat model of Alzheimer’s disease. Alzheimer's Research & Therapy. 2018;10(16):1-17. DOI: 10.1186/s13195-018-0346-2
• dc.identifier.doi http://dx.doi.org/10.1186/s13195-018-0346-2
• dc.identifier.issn 1758-9193
• dc.identifier.uri http://hdl.handle.net/10230/54241
• dc.language.iso eng
• dc.publisher BioMed Central
• dc.relation.ispartof Alzheimer's Research & Therapy. 2018;10(16):1-17
• dc.relation.isreferencedby https://doi.org/10.6084/m9.figshare.5867676.v1
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/278850
• dc.rights © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Alzheimer’s disease
• dc.subject.keyword Connectomics
• dc.subject.keyword Animal model
• dc.subject.keyword Magnetic resonance imaging
• dc.subject.keyword Resting state
• dc.subject.keyword Early biomarker
• dc.subject.keyword Transgenic
• dc.subject.keyword Rats
• dc.title Early brain connectivity alterations and cognitive impairment in a rat model of Alzheimer’s disease
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion