Abstract
Despite the acceleration of knowledge and data accumulation in neuroscience over the last years, the highly prevalent neurodegenerative disease of AD remains a growing problem. Alzheimer's Disease (AD) is the most common cause of dementia and represents the most prevalent neurodegenerative disease. For AD, disease-modifying treatments are presently lacking, and the understanding of disease mechanisms continues to be incomplete. In the present review, we discuss candidate contributing factors leading to AD, and evaluate novel computational brain simulation methods to further disentangle their potential roles. We first present an overview of existing computational models for 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 (www.thevirtualbrain.org), an open-source, multiscale, whole-brain simulation neuroinformatics platform. Finally, we discuss how this methodological approach may contribute to the understanding, improved diagnostics, and treatment optimization of AD.
Highlights
Every second senior with age above 90 years suffers from Alzheimer’s disease (AD) or another dementia (Robinson et al, 2018a)
This study showed how changes in regional dynamics could lead to the disintegration of activity within the anatomical large-scale brain network
We focus on The Virtual Brain, a multimodal and multiscale virtual brain simulation framework (Ritter et al, 2013; Sanz Leon et al, 2013; Sanz-Leon et al, 2015; Stefanovski et al, 2016; Solodkin et al, 2018) that holds the potential to combine different modeling scales of AD research
Summary
Every second senior with age above 90 years suffers from Alzheimer’s disease (AD) or another dementia (Robinson et al, 2018a). Alzheimer’s Disease and Brain Simulation rise as high as $1.1 trillion (Alzheimer’s Association, 2018) It is stated in the same report that early diagnosis at the stage of mild cognitive impairment (MCI) could save up to $7.9 trillion in cumulated medical and care costs by the year 2050. The brain has multiple organization levels (e.g., molecular, cellular, ensemble- and region-level), including both feedback and feedforward interactions between and within those different levels (Solodkin et al, 2018). These dependencies are non-linear, leading to emergent phenomena—features of the system that cannot be understood by the simple “sum” of its parts (Ritter et al, 2013).
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