From genes to network models of Alzheimer's disease: Biological framework for multi-scale brain simulation with The Virtual Brain

While the knowledge in neuroscience and the possibilities in clinical neurology have improved for many years, neurogenerative diseases and associated dementia remain a growing problem. Alzheimer’s Disease (AD) is the most common cause of dementia and also represents the most prevalent type of neurodegenerative diseases. For AD, disease-modifying treatments are presently lacking and the understanding of disease mechanisms remain incomplete. In the present review, we consider candidate contributing factors leading to AD and we evaluate novel computational brain simulation methods to further disentangle their potential roles. We first discuss existing computational models of AD that aim to provide a mechanistic understanding of the disease. Next, we outline the potential to link molecular aspects of neurodegeneration in AD with large-scale brain network modeling using The Virtual Brain (TVB, www.thevirtualbrain.org), an open-source, multi- scale, whole-brain simulation neuroinformatics platform. Finally, we discuss how this methodological approach may contribute to the understanding, improved diagnostics and treatment of AD.