Brain connectivity during Alzheimer's disease progression and its cognitive impact in a transgenic rat model

Abstract

The research of Alzheimer's disease (AD) in its early stages and its progression till symptomatic onset is essential to understand the pathology and investigate new treatments. Animal models provide a helpful approach to this research, since they allow for controlled follow-up during the disease evolution. In this work, transgenic TgF344-AD rats were longitudinally evaluated starting at 6 months of age. Every 3 months, cognitive abilities were assessed by a memory-related task and magnetic resonance imaging (MRI) was acquired. Structural and functional brain networks were estimated and characterized by graph metrics to identify differences between the groups in connectivity, its evolution with age, and its influence on cognition. Structural networks of transgenic animals were altered since the earliest stage. Likewise, aging significantly affected network metrics in TgF344-AD, but not in the control group. In addition, while the structural brain network influenced cognitive outcome in transgenic animals, functional network impacted how control subjects performed. TgF344-AD brain network alterations were present from very early stages, difficult to identify in clinical research. Likewise, the characterization of aging in these animals, involving structural network reorganization and its effects on cognition, opens a window to evaluate new treatments for the disease.

Instituto de Salud Carlos III (http://dx.doi.org/10.13039/501100004587), Award ID: PI14/00595. Emma Muoz-Moreno, Fundació la Marató de TV3 (http://dx.doi.org/10.13039/100008666), Award ID: 201441 10. FP7 Health, Award ID: FP7-HEALTH-2011.2.2.1-2. Instituto de Salud Carlos III (http://dx.doi.org/10.13039/501100004587), Award ID: PI18/00893, co-funded by ERDF, 'A way to make Europe'. Secretaria d'Universitats i Recerca del Departament d'Empresa I Coneixement de la Generalitat de Catalunya Award ID: AGAUR 2017 SGR 01003. European Community Award ID: FP7-HEALTH-2011.2.2.1-2, n 278850.